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THE  LIBRARY 

OF 

THE  UNIVERSITY 
OF  CALIFORNIA 

LOS  ANGELES 


RESEARCH    STUDIES    IN   PSORIASIS 


By 

JAY  F.[SCHAMBERG,  M.D.,  Director  of  the  Research; 
JOHN  A.  KOLMER,  M.D.,  Pathologist  and  Bacteriologist; 
A.    I.    RINGER,    M.D.,   and   G.    W.    RAIZISS,    Ph.D.,    Physiological 
Chemists. 


Reprinted  from  THE  JOURNAL  OF  CUTANEOUS  DISEASES,  INCLUDING  SYPHILIS, 
\  for  October  and  November,  1913. 


REBMAN,  COMPANY 

HERALD    SQUARE    BUILDING 

141-145  WEST  36TH  STREET 
NEW   YORK 


Bioir.edu:  al 
Library 

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2.05 


Reprinted  from  THE  JOUHXAL  or  CUTANEOUS  DISEASES,  IXCLUDINO  SYPHILIS, 
for  October  and  November,  1913. 


RESEARCH   STUDIES   IN   PSORIAISS 

A  PRELIMINARY    REPORT.* 

(From  the  Dermatological  Research  Laboratories  of  the  Philadelphia  Polyclinic 
and  College  for  Graduates  in  Medicine.) 

By 

JAY  F.  SCHAMBERG,  M.D.,  Director  of  the  Research; 
JOHN  A.  KOLMER,  M.D.,  Pathologist  and  Bacteriologist; 
A.    I.    RINGER,    M.D.,    and   G.    W.    RAIZISS,    Ph.D.,    Physiological 
Chemists. 

FOR  two  thousand  years  physicians  have  been  familiar  with  the 
clinical  appearances  of  psoriasis.  Much  is  known  of  its 
symptomatology,  its  course,  its  diagnosis,  its  histopathology 
and  not  a  little  concerning  its  local  treatment;  of  its  cause  and 
nature  however,  we  are  in  ignorance.  Auspitz  remarked  some  years 
ago — "Was  Psoriasis  ist,  weiss  bis  heute  noch  kein  Mensch." 

Through  the  philanthropy  of  a  generous  donor,  we  have  been 
enabled  to  inaugurate  at  the  Philadelphia  Polyclinic  and  College  for 
Graduates  in  Medicine,  a  research  investigation  into  the  nature  and 
treatment  of  psoriasis. 

It  is  obvious  that  a  research  into  the  nature  of  a  disease  should 
be  prosecuted  without  preformed  judgments  and  with  a  mind  free 
to  receive  impressions  from  the  results  of  experimental  work.  In  the 
investigations  that  have  been  carried  out,  no  attempt  has  been  made 
to  prove  any  theory  of  the  causation  of  psoriasis.  Two  lines  of 
inquiry  were  outlined — one  bacteriological  and  pathological,  and  the 
other  physiological-chemical ;  the  work  in  each  department  has  been 
carried  out  with  the  dominant  thought  of  recording  the  findings, 
whether  they  proved  to  be  of  a  positive  or  a  negative  character. 
In  this  manner  it  is  hoped  that  some  illumination  may  be  shed  upon  a 
*  Read  in  abstract  before  the  37th  Annual  Meeting  of  the  American  Derma- 
tological Association,  Washington,  D.  C.,  May  6-8,  1913. 


63586S 


2         SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

disease,  concerning  whose  nature  the  widest  divergence  of  opinion 
exists,  and  yet  of  which  we  know  definitely  no  more  than  did  Hip- 
pocrates. 


PART    I. 
PATHOLOGY. 

CONCERNING  COMPLEMENT  FIXATION  IN  PSORIASIS. 

The  original  conception  and  explanation  of  the  Wassermann  re- 
action in  syphilis,  as  being  an  example  of  complement  fixation 
through  the  interaction  of  a  specific  antigen  and  its  antibody,  is  now 
generally  regarded  as  untenable.  This  reaction  occupies  a  unique 
position  owing  to  the  fact  that  the  "antigen"  in  the  reaction  need 
not  be  the  Treponema  pallidum  but  any  suitable  lipoid.  The  essen- 
tial factor  is  the  presence  in  the  body  fluids  of  a  reactionary  product 
of  cellular  activity,  "a  reagin,"  due  to  infection  with  Treponema 
pallidum,  which  possesses  as  a  chief  characteristic  a  marked  affinity 
for  lipoids  and  is  capable,  in  the  presence  of  a  suitable  lipoid,  of  in- 
activating complement  in  the  test  tube,  the  phenomenon  being  better 
known  as  complement  fixation.  Similar  lipoidophilic  "antibodies" 
are  to  be  found  in  the  body  fluids  of  persons  infected  with  leprosy 
and  yaws.  The  latter  is  also  a  spirochsetal  infection  while  the  exact 
nature  of  the  microorganism  of  leprosy  is  unsettled.  It  is  of  signifi- 
cant importance,  however,  that  certain  parasites  possess  the  power 
of  stimulating  the  production  of  this  peculiar  lipoidophilic  "reagin," 
best  seen  in  luetic  infection  and  thus  the  investigation  of  diseases  of 
unknown  aetiology  by  a  study  of  complement  fixation,  using  a  lipoid 
as  "antigen,"  offers  the  possibility  of  shedding  some  light  upon  the 
nature  of  the  antibodies  and  possibly  upon  the  question  of  para- 
sitism. 

Among  other  infections,  however,  examples  of  specific  complement 
fixation  through  the  interaction  of  antigen  and  its  amboceptor  are 
well  known.  Of  serum  reactions,  that  of  complement  fixation  is 
probably  the  most  exact  for  demonstrating  the  presence  of  anti- 
bodies due  to  the  activities  of  bacterial  or  other  protein  substances 
and,  therefore,  if  the  antigen  is  known  the  antibody  may  be  found, 
or,  conversely,  if  the  antibody  is  present  in  the  tissues  and  body 
fluids  the  specific  antigen  may  be  found  by  complement  fixation  ex- 
periments with  different  substances  supposed  to  contain  the  specific 


RESEARCH    STUDIES    IN    PSORIASIS  3 

antigen.  In  this  manner  we  were  led  to  study  the  question  of  local 
parasitism  in  psoriasis  by  preparing  extracts  of  the  scales  and  of 
various  cultures  of  bacteria  isolated  from  psoriatic  lesions,  with  the 
idea  of  determining  their  setiological  relationship  by  specific  com- 
plement fixation  with  the  sera  of  psoriatic  persons,  based  upon  the 
possibility  that  a  specific  immune*  amboceptor  was  present  in  the 
sera  of  such  subjects.  These  reactions,  however,  have  distinct  limi- 
tations ;  even  in  pneumonia,  tuberculosis,  etc.,  where  the  specific  anti- 
gen is  known,  inconstant  results  are  obtained.  It  is  to  be  remem- 
bered, therefore,  in  this  connection,  that  while  positive  results  are  of 
considerable  value,  negative  results  do  not  necessarily  mean  that  the 
specific  antigen  is  absent  from  the  extracts  of  infected  tissues  used 
in  the  reactions. 

The  object  of  this  study  was  mainly  two- fold: 

1.  To  apply  the  Wassermann  reaction  to  the  study  of  psoriasis, 
to  ascertain  the  presence  or   absence    of  lipoidophilic   antibodies 
(reagin). 

2.  To  study  complement  fixation  with  the  sera  of  psoriatic  pa- 
tients, using  extracts  of  scales   and  organisms   cultured  from  the 
lesions,  with  the  view  of  shedding  light  on  the  question  of  parasitism. 


THE  WASSERMANN  REACTION  IN  PSORIASIS. 

The  available  literature  bearing  upon  this  question  is  quite 
meagre.  1.  Gjorjevic  and  Savnik1  studied  the  reaction  with  sera  of 
20  patients,  using  an  alcoholic  extract  of  guinea  pig  heart  as  anti- 
gen. One  of  their  cases  gave  a  history  of  lues  and  must,  therefore, 
be  excluded  from  the  series.  Of  the  24  remaining  cases  giving  nega- 
tive histories  of  luetic  infection,  20  yielded  weakly  positive  reactions. 
In  one  case  the  reaction  was  found  positive  with  active  and  negative 
with  inactive  serum ;  2  cases  giving  weak  positive  reactions,  reacted 
negatively  after  treatment.  2.  Bruck2  questioned  these  results,  re- 
porting negative  results  with  both  active  and  inactive  sera  in  42 
psoriasis  cases  of  45  examined.  The  remaining  3  cases  were  strongly 
positive,  but  gave  positive  histories  of  luetic  infection.  However,  it 
should  be  mentioned  that  he  did  not  consider  as  positive,  reactions 
showing  a  weak  or  slight  degree  of  inhibition  of  haemolysis. 

1  GJOKJEVIC,   G.,   and   SAVNIK,   P.    Wien.    klin.    Wchnsch.,    1910,  xxii,   No.    17, 
p.  626. 

2  BHUCK,  C.     Wien.  klin.  Wchnschr.,  1910,  xxii,  No.  19,  p.  704. 


4         SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

TECHNIQUE. 

1.  ANTIGENS. — Owing  to  the  observation  that  the  lipoidophilic 
"reagin"  in  syphilis   apparently   varies   in  its  affinity   for  various 
lipoids,  it  is  advisable  to  use  several  extracts  with  each  serum  in  con- 
ducting the  Wassermann  syphilis  reaction.     For  this  reason  we  have 
used  the  following  extracts  in  studying  the  sera  of  48  patients : 

(a)  alcoholic  extract  of  syphilitic  liver; 

(b)  acetone  extract  of  syphilitic  liver; 

(c)  acetone  insoluble  lipoids; 

(d)  alcoholic  extract  of  guinea  pig  heart; 

(e)  cholesterinized  alcoholic  extracts  of  beef  and  human  heart. 
All  of  these  extracts  were  titrated  for  their  antigen ic  unit  with 

the  serum  of  a  case  of  secondary  syphilis.  In  conducting  the  re- 
actions, double  the  titrated  dose  was  used,  providing  that  this 
amount  was  at  least  eight  to  ten  times  less  than  the  anticomplemen- 
tary  dose. 

2.  COMPLEMENT. — Fresh  guinea  pig  serum  was  diluted  1 :20  and 
used  in  a  dose  of  one  unit  after  titration  with  one  unit  of  ambo- 
ceptor, carried  over  from  week  to  week  or  used  in  a  dose  of  1  cc.  and 
the  amboceptor  titrated  with  this  dose  and  1  cc.  of  a  2.5%  suspension 
of  washed  sheep  corpuscles. 

3.  H^MOLYTIC  AMBOCEPTOR. — Antisheep  rabbit  amboceptor  was 
used  in  doses  representing  one  hsemolytic  unit.     This  is  an  important 
feature  of  the  technique,  for  the  quantitative  relationship  between 
complement  and  amboceptor  is  quite  important,  an  excess  being  able 
to  mask  weakly  positive  reactions.    The  exact  adjustment  of  comple- 
ment and  amboceptor  is  especially  desirable  when  using  the  sheep 
hiemolytic  system,  owing  to  the  presence  of  varying  quantities  of 
natural  antisheep  amboceptor  in  human  sera. 

4.  SERUMS. — Sera  were  inactivated  by  heating  to  55°  C.  for  one 
half  hour.    Doses  of  from  0.1  to  0.2  cc.  were  employed. 

5.  CORPUSCLES. — One  cc.  of  washed  sheep  corpuscles  in  2.5% 
suspension.     Since  all  sera  were  tested  with  3  to  5  different  "anti- 
gens" at  the  same  time,  the  usual  quantities  of  the  various  compo- 
nents of  the  syphilis  reaction  were  used  in  half  the  amounts  of  the 
original  Wassermann  reaction. 

Serum,  antigen  and  complement  were  diluted  to  3  cc.  with  sterile 
normal  salt  solution  and  incubated  at  37°  C.  for  one  hour;  1  cc.  of 
the  corpuscle  suspension  and  one  hasmolytic  dose  of  amboceptor  were 
added  and  tubes  reincubated  for  one  to  two  hours,  depending  upon  the 
ha-molysis  of  the  controls.  Tubes  were  then  placed  in  the  refrig- 
erator over  night,  readings  being  made  and  recorded  next  morning. 

For  controls :  the  serum  of  each  patient  without  antigen ;  a  luetic 
and  a  normal  serum  with  each  "antigen";  complement;  corpuscle; 
amboceptor  and  haemolytic  controls  were  set  up  each  time. 


RESEARCH    STUDIES    IN    PSORIASIS 


RESULTS. 

The  results  of  the  investigation  of  48  sera  are  given  in  the  follow- 
ing table: 

TABLE    I. 
WASSEBMANN  REACTION  IN  PSORIASIS. 


Case.    Name. 


1.  U— h 

2.  M — n 

3.  Q— y   : 

4.  F— n   . 

5.  M — s   . 

6.  P— s  . 

7.  L— f  . 

8.  S—r   . 

9.  C— y  . 

10.  R— d  . 

11.  C— k   . 

12.  P— e    . 

13.  N— n  . 

14.  D— y  . 

15.  B— n   . 

16.  S— b    . 

17.  B— b   . 

18.  S— p  . 

19.  C— n   . 

20.  D— y  . 

21.  C— t  . 

22.  M— y  . 

23.  K— g  . 

24.  S— m 

25.  C— e  . 

26.  H— n 

27.  Me— n 

28.  Me — e 

29.  A— n  . 

30.  F— n   . 

31.  B — n  . 

32.  L— a   . 

33.  C— a    . 

34.  D— h  . 

35.  B— n  . 

36.  D— s    . 

37.  M— a  . 

38.  L— f    . 

39.  R— n  . 

40.  B— n   . 

41.  T— t  ., 

42.  F— m    . 

43.  S— s    . 


ANTIGENS. 

Alcoholic         Acetone  Acetone      Alcoholic 

Syph.  liver.    Syph.  liver.      InsoL  Lip.    Pig  Heart. 


Cholest. 
heart. 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

0 

9 
0 
0 
0 
0 
0 
0 


6         SCHAMBERG,  KOLMER,  RIXGER,  AND  RAIZISS 

TABLE  I.— Continued. 
WASSKHMANU    REACTION   IN   PSORIASIS. 

ANTIGENS. 

Alcoholic        Acetone         Acetone        Alcoholic         Cbolest. 
Name>         Syph.  liver.    Syph.  liver.      Insol.  Lip.      Pig  Heart.         heart. 

44.  C— e   

45.  H— d +  +  0  0  + 

46.  R— r    0  + 

47.  J—y   +  +  +  0  +  + 

48.  M— s   0 

0  indicates  that  the  particular  antigen  so  marked  was  not  employed. 
-  indicates  complete  haemolysis  (negative  reaction). 
±  indicates  ,less  than  25%  inhibition  of  haemolysis  (doubtful  reaction). 
+  indicates  25%  inhibition  (weakly  positive). 
-J-+  indicates  50%  inhibition  (positive  reaction). 
-|--|--r-  indicates  75%  inhibition  (strongly  positive  reaction). 
-f--| — (--(-  indicates  100%  or  absolute  inhibition  of  haemolysis. 

An  examination  of  the  table  shows  the  number*  and  degree  of 
positive  reactions.  The  histories  of  those  reacting  positively  will  be 
given  later.  It  is  to  be  noted  that  the  occurrence  and  degree  of 
positive  reactions  varied  with  the  different  "antigens"  and  these  are 
worthy  of  further  analysis: 

1.  With  the  alcoholic  extracts  of  syphilitic  liver,  9,  or  18.7%  of 
sera  reacted  positively  as  follows : 

(a)  Two  cases  yielded  less  than  25%  inhibition  (±). 

(b)  Two  yielded  weakly  positive  reactions  (  +  ). 
•(c)   Four  gave  positive  reactions  (-}--|-). 

(d)   One  gave  strong  inhibition  of  haemolysis  or  (-f--|--}-). 

In  this  study  several  alcoholic  extracts  of  luetic  liver  were  used, 
including  German  products  standardized  by  Wassermann  and  Meier. 

2.  With  the  acetone  extract  of  syphilitic  liver,  9  or  18.7%  of 
sera  reacted  positively,  all  being  with  the  same  sera  that  reacted 
positively  with  the  alcoholic  extract  of  syphilitic  liver. 

8.  With  an  extract  of  acetone  insoluble  lipoids,  45  sera  were 
examined,  positive  reactions  occurring  in  6,  or  13.3%  of  cases  as 
follows : 

(a)  One  case  showed  25%  inhibition  of  haemolysis  (+)• 

(b)  Five  cases  yielded  50%  inhibition  (  +  +  ). 

It  is  to  be  noted,  however,  that  the  difference  in  percentage  of 
positive  reactions  with  this  extract  compared  with  the  results  with 
alcoholic  extracts  of  luetic  liver  is  due  to  the  fact  that  not  all  cases 
were  tested  with  the  extracts  of  acetone  insoluble  lipoids.  In  every 
instance  where  a  positive  reaction  occurred  with  the  alcoholic  ex- 


RESEARCH    STUDIES    IN    PSORIASIS  7 

tract  of  luetic  liver,  a  positive  result  likewise  resulted  with  acetone 
insoluble  lipoids. 

4.  Thirty  serums  were  tested  with  an  alcoholic  extract  of  guinea 
pig  heart,  positive  reactions  occurring  in  5  instances,  the  reaction 
with  an  alcoholic  extract  of  syphilitic  liver  being  likewise  positive  in 
each  case. 

5.  With  cholesterinized  alcoholic  extracts  of  human  beef  heart, 
the  percentage  of  positive  reactions  was  higher,  for  in  4  instances 
these  extracts  yielded  positive  reactions  with  sera  which  were  nega- 
tive with  alcoholic  and  acetone  extracts  of  luetic  liver  and  an  ex- 
tract  of  acetone  insoluble  lipoids.     Thus,   of  22  sera  tested  with 
cholesterinized  extracts,  8,  or  36.3%  reacted  positively  as  follows: 

(a)  One  case  yielded  less  than  25%  inhibition  (±). 

(b)  Two  cases  gave  25%  inhibition  (-{-). 

(c)  Five  cases  gave  50%  inhibition  (-f — (-). 

As  pointed  out  by  Kolmer3  and  his  associates,  cholesterinized  ex- 
tracts, especially  cholesterinized  alcoholic  extract  of  beef  heart,  may 
yield  25%  or  less  inhibition  of  haemolysis  with  about  10%  of  normal 
sera.  For  this  reason  it  is  a  difficult  matter  to  properly  interpret 
the  results  if  using  cholesterinized  extracts  alone,  when  conducting 
the  Wassermann  reaction.  This  is  additional  evidence  in  support  of 
the  necessity  of  using  several  extracts,  plain  and  cholesterinized,  with 
each  serum  tested  for  the  presence  of  syphilis  reagin. 

In  4  cases  yielding  positive  reactions  with  the  cholesterinized  and 
negative  reactions  with  plain  extracts,  the  degree  of  the  reactions 
was  as  follows : 

(a)  Case  46,  R.,  less  than  25%  inhibition  (±). 

(b)  Case  37,  M— a.,  25%  inhibition  (+)• 

(c)  Cases  40  and  43,  50%  inhibition  (+  +  )- 

Omitting  Cases  46  and  37  as  possible  inhibitions  of  haemolysis 
with  cholesterinized  extracts  and  normal  sera,  it  leaves  2  cases  (40 
and  43)  in  which  this  possibility  is  not  likely,  as  controlled  by  the  use 
of  these  same  extracts  in  a  large  number  of  cases  of  lues,  the  results 
being  given  in  the  paper  by  Kolmer,  already  alluded  to.  Of  the  48 
cases  examined  it  is  found,  therefore,  that  slight  reactions  occurred 
in  18.7%  of  cases  with  an  alcoholic  extract  of  luetic  liver,  and  of 
22  cases  in  28.5%  with  the  cholesterinized  extracts,  as  antigens. 

In  5  of  our  cases  an  opportunity  was  afforded  for  repeating  the 

3  KOLMER,  J.  A.,  LAUBAUGH,  E.  E.,  CASSELMAN,  A,  J.,  and  WILLIAMS,  "W.  W. 
"Practical  Studies  on  the  So-called  Syphilis  'Antigens,'  with  Special  Reference  to 
Cholesterinized  Extracts."  Arch.  Int.  Med.  (in  press). 


8         SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

reactions  at  a  subsequent  time.  While  in  a  few  of  these  patients 
improvement  had  taken  place,  yet  some  reaction  was  present.  In  all 
of  the  cases  the  complement  fixation  reactions  were  practically  the 
same  as  in-  the  first  test. 

TABLE    II. 
REPEATED  WASSEKMANN   REACTIONS  IN  PSORIASIS. 

Alcoholic      Acetone        Acetone      Alcoholic 
d'Syph.  liver.  Syph.  liver.  Insol.  Lip.  Pig  Heart. 

1 .  U— h 8  mos. 

2 .  M — m ....     4  mos. 
2.     M — n  ....     8  mos. 

1 5 .     B — in  ....     1  mo. 

43.     S — s    1  mo. 

46.     R— r 1  mo. 

INTERPRETATION  OF  RESULTS. 

It  is  most  remarkable  that  there  should  have  been  9  cases  of 
psoriasis  out  of  48  or  18.7%  that  have  reacted  positively  with  the 
complement  fixation  test  employing  the  Wassermann  antigen  (alco- 
holic extract  of  luetic  liver).  We  cannot,  with  Bruck,  brush  these 
results  aside  and  accord  no  significance  to  them,  because  the  reactions 
were  weak,  for  some  of  our  reactions  were  of  medium  degree.  In  4 
out  of  the  9  cases  there  was  50%  of  inhibition  of  haemolysis  and  in 
one  75%.  Moreover,  in  the  reactions  made  with  cholesterinized  anti- 
gens, in  which  we  have  considerable  confidence  within  the  limita- 
tions expressed  by  us,  over  28%  of  the  22  cases  examined  gave  posi- 
tive reactions. 

In  Case  15,  it  is  quite  possible  that  the  patient  may  have  been 
a  luetic  subject,  as  there  is  a  history  of  a  "chancroid"  and  a  subse- 
quent history  which  is  not  devoid  of  some  suspicion.  Cases  1  and 
2  were  men  who  presented  no  evidence  whatsoever  of  lues  and  who 
firmly  denied  any  history  of  infection.  Cases  4  and  28  were  re- 
spectable young  single  women,  presenting  no  evidence  of  acquired 
or  hereditary  lues. 

Case  33  was  a  married  woman  who  had  two  miscarriages,  but 
has  two  healthy  children,  one  born  between  the  miscarriages. 

There  did  not  appear  in  our  patients  to  be  any  definite  relation 
between  the  severity  of  the  psoriasis  eruption  and  the  Wassermann 
reaction.  Four  cases  giving  positive  reactions  were  severe  cases,  but 
several  were  very  mild.  Several  other  severe  cases  gave  negative 
reactions. 

We  cannot  feel,  from  a  clinical  study  of  the  patients  whose  reac- 


RESEARCH    STUDIES    IN    PSORIASIS  9 

tions  are  here  presented,  that  the  positive  serum  tests  can  all  be 
attributed  to  syphilis,  although  this  might  be  true  of  a  few  of  them. 
On  the  other  hand,  some  significance  must  be  attached  to  them,  which 
future  research  alone  can  reveal.  We  are  content  for  the  present  to 
report  the  facts  without  attempting  to  suggest  an  interpretation  of 
them. 

PART    II. 

A.     COMPLEMENT  FIXATION  EXPERIMENTS  IN  PSORIASIS  WITH  SCALES 
AND  CULTURE  ANTIGENS. 

As  already  stated,  these  were  undertaken  with  the  assumption  that 
if  an  antibody  existed  in  psoriasis  it  was  in  the  nature  of  an  ambo- 
ceptor  and  present  in  the  body  fluids  of  psoriasis  patients  in  demon- 
strable amount.  If  this  were  true  and  if  the  antigen,  presumably  a 
parasite,  were  present  in  the  scales  or  happened  to  be  among  the 
organisms  isolated  in  pure  culture  from  psoriatic  lesions,  suitable 
extracts  of  these  should,  with  the  antibody  inactivate  complement,  or 
in  other  words,  yield  positive  complement  fixation  reactions. 

TECHNIQUE. 

1.  ANTIGENS. — The  following  antigens  were  prepared  and  used 
in  this  study: 

No.  1.  NaCl  extract  of  scales.  The  scales  of  three  cases  were 
lightly  washed  and  dried.  Five  grams  were  ground  with  quartz  sand 
and  treated  with  50  cc.  of  .85%  salt  solution  containing  0.5%  phenol. 
This  mixture  was  shaken  automatically  for  six  hours ;  extracted  at 
37°  C.  for  48  hours ;  filtered  and  titrated. 

No.  2.  Alcoholic  extracts  of  scales.  Five  grains  of  scales  were 
ground  and  treated  with  50  cc.  pure  alcohol;  shaken  automatically 
for  six  hours ;  extracted  at  37°  C.  for  48  hours  ;  filtered  and  titrated. 

No.  3.  NaCl  culture  antigen.  Pure  cultures  of  twelve  different 
species  of  organisms  isolated  from  psoriatic  lesions  were  grown  on 
glucose  agar;  washed  off  with  NaCl  solution;  shaken  automatically 
for  two  hours;  heated  to  60°  C.  for  one  hour;  1%  phenol  and  gly- 
cerine were  added ;  titrated. 

No.  4.  Cultures  were  made  and  washed  off  with  NaCl  solution  as 
in  preparing  antigen  No.  3.  The  emulsion  was  treated  with  equal 
volume  of  absolute  alcohol  and  centrifuged;  the  supernatant  fluid 
was  decanted  and  the  precipitate  dried  over  calcium  chloride,  ac- 
curately weighed  and  ground  with  sufficient  sodium  chloride  crystals 
to  make  up  a  2%  suspension  of  the  ground  organisms  in  .85%  salt 
solution.  The  relative  amounts  of  dried  organisms  used  were  as 
follows : 


10       SCHAMBERG,  KOLMER,  RINGER,  AXD  RAIZISS 


1 
1 
1 
1 
1 
1 
1 

cc. 
cc. 
cc. 
cc. 
cc. 
cc. 
cc. 

diluted 
diluted 
diluted 
diluted 
diluted 
diluted 
diluted 

1 
1 
1 
1 
1 
1 
1 

:10 
:20 
:40 
:80 
:160 
:S20 
:640 

=  2.0  mg. 
=  1.0  mg. 

=  0.5  nig. 
=  0.25  mg. 
=  0.125  mg. 
=  0.062  mg. 
=  0.031  mg. 

Before  using  this  antigen  with  sera  all  the  above  doses  were 
tested  for  anticomplementary  dosage.  It  was  found  that  all  but  the 
largest  dose  were  free  of  anticomplementary  effect  and  consequently 
were  used  with  the  various  serums. 

No.  5.  A  salt  solution  extract  was  also  prepared  of  two  ascites 
kidney  agar  cultures  of  pieces*  of  psoriasis  skin  as  follows :  The  oil 
and  kidney  were  removed  and  ascites  agar  columns  were  weighed, 
ground  with  quartz  sand  and  treated  with  5  volumes  of  salt  solution. 
This  emulsion  was  then  heated  to  60°  C.  for  an  hour  and  0.5% 
phenol  added. 

Three  different  sets  of  antigens  were  prepared  and  used  with  a 
number  of  sera  from  psoriasis  patients.  All  antigens  were  titrated 
for  anticomplementary  dose  and  one  quarter  of  this  amount  used  as 
an  antigenic  dose  in  conducting  the  reactions. 

The  following  table  gives  the  results  of  such  titrations  with  one 
set  of  antigens. 

TABLE    III. 
ANTICOMPLEMENTAKY  POWER  OF  ANTIGENS. 


Amount  of 


Antigens. 


antigen. 

1. 

2. 
Oil.  1:20 

3. 
Dil.  1:10 

5. 

Dil.  1:10 

01    cc     

H. 

H. 

H. 

H. 

02   cc     

H. 

H. 

H 

H 

0  4   cc         

H. 

H. 

H 

H 

0  8   cc         

S.I.H. 

H. 

H 

M  I  H 

1  0   cc         

M.I.H. 

S.I.H. 

M  I.H. 

I  H 

1.5   cc  

I.H. 

M.I.H. 

I.H. 

I.H 

20   cc  

l.H. 

I.H. 

I.H. 

I.H. 

3.0   cc  

I.H. 

l.H. 

I.H. 

I.H 

Antigenic    dose 
used    

0.2  cc. 

0.2  cc. 

0.3  cc. 

0.2  cc. 

H.  =  complete  haemolysis. 
S.I.H.  =  slight  inhibition  of  haemolysis. 
M.I.H.  =  marked  inhibition  of  haemolysis. 
I.H.  =  inhibition  of  haemolysis. 


RESEARCH    STUDIES    IN    PSORIASIS 


11 


2.  Haemolytic    System.     The   antisheep   sheep   system   was    em- 
ployed in  the  same  manner  as  in  the  Wassermann  reaction. 

3.  Patients'  Serum.     The  sera  of  ten  persons  suffering  with  ex- 
tensive psoriasis  were  used.     All  sera  were  inactivated  by  heating 
to  55°  C.  for  30  minutes  and  used  in  ascending  doses :  .01  cc.,  .04  cc., 
.08  cc.,  0.1  cc.  and  0.3  cc. 

4.  Controls.  The  maximum  dose  of  serum  (0.3  cc.)  without  anti- 
gen ;  haemolytic,  complement,  antigen  and  corpuscle  controls  as  usual. 

The  sera  of  10  psoriatic  persons  were  tested  with  all  antigens. 
The  following  table  of  results  with  one  serum  shows  the  method  used. 

TABLE    IV. 

RESULTS  OF  COMPLEMENT  FIXATION  REACTIONS  WITH  PSORIASIS  SERUM  AND 
VARIOUS  ANTIGENS. 


Amount   of 
Serum. 

Antigens. 

No.  1. 
0.2  cc. 

No.  2. 
0.2  cc. 

No.  3. 

0.3  cc. 

No.  5. 
0.2  cc. 

.0]    cc  

H. 
H. 
H. 
H. 
H. 
S.I.H. 

H. 
H. 
H. 
H. 
H. 
H. 

H. 
H. 
H. 
H. 
H. 
M.I.H. 

H. 
H. 
H. 
H. 
S.I.H. 
M.I.H. 

.04  cc  

.08  cc  

.1    CC  

.2  cc  •. 

3  cc  

Control   .3   cc.. 

None 

None 

None 

None 

With  antigen  No.  4,  the  serums  were  used  in  constant  dose  of  0.2 
cc.  with  ascending  doses  of  antigen  as  follows:  .031  mg.,  .062  mg., 
0.125  mg.,  0.25  mg.,  0.5  mg.  and  1.0  mg. 


RESULTS. 

Nine  other  sera  from  active  cases  of  psoriasis,  three  of  which 
yielded  slightly  positive  Wassermann  reactions  with  lipoidal  ex- 
tracts, were  tested  in  the  above  manner  with  all  antigens.  In  no 
instance  was  there  a  complement  fixation  reaction  which  could  be 
regarded  as  a  specific  reaction. 

After  repeating  these  experiments  three  times,  we  feel  quite  cer- 
tain that  either  the  true  antigen  was  not  present  in  the  extracts  of 
scales  and  cultures  used  or  that  the  psoriasis  antibody  if  it  exists,  was 
not  present  in  the  sera  in  sufficient  amount  to  inactivate  complement 
with  the  extracts  used  in  this  study. 


12       SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

B.     BACTERIOLOGY. 

LITERATURE 

Various  organisms  and  "bodies"  have  been  described  from  time 
to  time  as  the  possible  cause  of  psoriasis,  but  none  has  been  ade- 
quately confirmed  by  other  investigators  or  accepted  by  competent 
critics.  As  early  as  1856,  Horing  (Med.  Correspondenzbl.  d.  Wurtt. 
Acrztl.  Verein.,  1856,  p.  149)  and  Hafner  (Ibid.,  p.  2541),  reported 
cases  of  psoriasis  conveyed  from  cattle  to  human  beings ;  they  sought 
for  the  parasite  without  result.  From  the  description  given,  the 
affection  observed  is  generally  believed  to  be  "ringworm." 

Wertheim  in  1853  (  Abstr.  Gaz.  hebd.  de  med.,  p.  449),  examined 
the  blood  of  psoriasis  patients  for  microorganisms  and  failing  to  find 
any,  studied  the  urine,  in  which  he  discovered  a  fungus  of  the  Peni- 
cillium  glaucum  species,  with  which  he  carried  out  animal  inocula- 
tions. 

In  1879,  Lang  (Vrtljschr.  f.  Dermal,  u.  Syph.,  1879,  p.  257), 
described  in  psoriasis  scales  a  hyphomycete  consisting  of  spores  and 
mycelium  which  he  termed  "epidermidophyton."  Eklund,  in  1883 
(Ann.  de  dermat.  et  de  syph.,  1883,  No.  4),  found  a  similar  fungus 
which  he  designated  "Lepocolla  repens." 

Rics,  of  Strassburg,  in  1888,  in  a  splendid  series  of  papers,  dis- 
posed of  these  claims  by  proving  that  the  so-called  parasites  were  in 
reality  artefacts  produced  by  the  action  of  the  potassium  hydrate 
solutions  used  in  the  examination  of  the  scales. 

In  1887,  the  question  of  the  parasitism  of  psoriasis  was  discussed 
at  the  Italian  Congress  of  Pavia.  De  Matei  found  a  micrococcus 
which  he  regarded  as  the  cause  of  psoriasis;  inoculations  of  this 
organism  upon  animals  produced,  he  alleged,  psoriasis-like  efflores- 
cences. Majocchi  looked  upon  De  Matei's  findings  as  accidental. 

INOCULATION  EXPERIMENTS. — In  1885,  Lassar  (Berl.  klin. 
Wchmchr.,  1885,  No.  47,  p.  771),  demonstrated  before  the  Berliner 
medizinische  Gesellschaft,  two  rabbits  that  he  had  inoculated  with 
psoriasis.  One  was  inoculated  with  the  scales,  lymph  and  blood  from 
a  psoriatic  patient  and  the  second  rabbit  from  the  resulting  lesion 
in  the  first.  In  both  animals  there  was  loss  of  hair  at  the  inoculated 
site  and  in  the  first  animal  redness,  thickening  of  the  skin  and  a  heap- 
ing up  of  scales.  The  removal  of  the  coarse  scales  led  to  capillary 
h/rmorrhage.  Lassar  stated,  however,  that  further  research  along 
these  lines  was  necessary  before  he  would  draw  any  binding  conclu- 
sions as  to  the  transmissibility  of  psoriasis.  Behrend,  who  was  pres- 
ent at  the  demonstration,  said  that  the  lesions  did  not  conform  to 
psoriasis  in  the  human  subject;  they  resembled  more  herpes  ton- 
surans. 


RESEARCH    STUDIES    IN    PSORIASIS  18 

Ducrey  (Sulla  voluta  contagiosita  della  psoriasi,  Gior.  ital.  d. 
mal.  veil.,  1887,  No.  6,  abstr.  Arch.  f.  Dermat.  u.  Syph.,  1888,  p. 
425),  tried  numerous  experiments  on  man  and  upon  rabbits,  guinea 
pigs  and  dogs,  to  test  the  transmissibility  of  psoriasis.  His  experi- 
ments consisted  of  (1)  vigorous  inunction  of  a  mixture  of  psoriasis 
scales  with  the  lymph  and  blood  that  exuded,  into  normal,  abraded 
and  incised  skin.  (2)  Application  of  the  same  to  a  blistered  area. 
(3)  Hypodermatic,  rectal,  intraperitoneal  and  intratracheal  injec- 
tion of  psoriatic  diseased  products.  All  of  the  results  were  negative. 
Ducrey  concluded  that  (1)  psoriasis  is  not  transmissible  either  to 
man  or  lower  animals;  (2)  the  various  forms  of  parasites  found  by 
different  persons  in  psoriasis  lesions  are  in  all  probability  not  the 
cause  of  psoriasis. 

De  Amicis  and  Campana  also  inoculated  rabbits  and  guinea  pigs 
with  entirely  negative  results. 

INOCULATIONS  ON  MAN. — In  addition  to  the  negative  inocula- 
tions upon  man  carried  out  by  Ducrey,  Alibert  and  De  Amicis,  Ham- 
mer and  Block  have  attempted  the  same  experiments  without  results. 
Wutzdorff's  effort  to  inoculate  himself  was  unsuccessful. 

With  scales  and  lymph  from  a  well-pronounced  case  of  psoriasis 
in  a  young  man,  Schamberg  (Jour.  Cutan.  Dis.,  Nov.,  1909)  inocu- 
lated an  abraded  area  upon  the  flexor  surface  of  his  forearm.  The 
inoculation  was  entirely  negative. 

Inoculation  experiments  upon  man  and  lower  animals  may  be 
said  to  have  all  failed  with  the  single  exception  of  Destot,  who  was 
apparently  successfully  inoculated  from  a  case  of  post-vaccinal 
psoriasis. 

In  approaching  the  study  of  psoriasis  from  the  bacteriological 
standpoint,  several  possibilities  are  to  be  considered:  The  disease,  if 
parasitic  (a),  might  be  due  to  the  implantation  upon  the  skin  of  an 
exogenous  parasite,  as  is  observed  in  ringworm,  fayus  and  tinea 
versicolor.  Such  an  organism  has  hitherto  not  been  found,  but  might 
be  discoverable  by  the  use  of  the  ultramicroscope  or  by  some  new 
technique,  (b)  The  disease  might  be  caused  by  one  of  the  common 
facultative  organisms  belonging  to  the  group  of  cocci,  so  readily 
cultivable  from  the  skin,  in  individuals  in  whom  the  soil  is  rendered 
favorable  by  some  special  condition,  (c)  The  disease  might  be  the 
result  of  the  circulation  in  the  fluids  of  the  body  and  deposition  in 
the  skin  of  a  microparasite,  analogous  to  what  is  observed  in  syphilis 
and  variola. 

The  successful  accomplishment  of  inoculation  would  go  far 
toward  establishing  the  parasitic  nature  of  the  disease  and  facilitate 
bacteriological  research. 


14-       SCHAMHKKG,   KOLMKR,  RINGER,  AND  RAIZISS 

Various  cocci  and  to  a  lesser  extent,  bacilli,  are  to  be  found 
among  the  more  common  bacteria  of  the  skin.  The  classification  of 
these  is  quite  difficult,  and  at  the  present  time  considerable  confusion 
exists,  so  that  each  investigator  has  come  in  time  to  adopt  his  own 
classification. 

From  the  fact  that  the  skin,  especially  the  exposed  parts,  is  sub- 
ject to  contamination  with  air,  water,  etc.,  it  becomes  more  difficult 
to  determine  just  which  species  belong  properly  to  the  skin  as  their 
natural  habitation  and  which  represent  contamination. 

The  original  classification  of  Unna  and  Tommasoli  (Flora  der- 
matologica,  Monatsh.  f.  prakt.  Dermat.,  iv,  No.  2,  p.  49)  was 
based  largely  upon  morphology,  growth  in  gelatin  and  shape  of 
colonies  in  agar-agar  and  gelatine  plates.  With  these  methods  they 
divided  the  various  cocci  in  separate  species.  Since  then  other  in- 
vestigators would  group  all  cocci,  including  diplococci,  in  one  gen- 
eral class  without  endeavoring  to  separate  species. 

Several  points  in  this  connection  should  be  borne  in  mind.  First, 
an  organism  cannot  be  properly  classified  upon  one  cultivation  alone. 
Thus  a  culture  of  diplococci,  when  freshly  isolated  may  be  distinctly 
gonococcoid  in  shape ;  not  a  few  of  such  cultures  lose  this  character 
in  later  sub-cultures,  the  cocci  dividing  into  twos  and  threes  with  the 
line  of  cleavage  poorly  defined.  The  shape  and  character  of  colonies 
in  agar  is  not  entirely  reliable,  because  the  age  of  the  colony  and  its 
depth  in  the  agar  materially  alter  its  shape  and  morphological  char- 
acters. The  same  is  true  of  gelatine,  only  here  the  presence  or  ab- 
sence of  liquefaction  has  decidedly  more  value. 

Probably  the  behavior  of  the  various  cocci  in  gelatine  and  milk 
has  most  value  in  classification.  It  is  to  be  remembered,  however, 
that  the  age  of  the  culture  is  an  important  factor;  thus,  some  cul- 
tures liquefy  gelatine  or  coagulate  milk  very  slowly  indeed,  but  never- 
theless are  liquifiers  and  coagulators.  This  difference  between  cul- 
tures of  cocci  renders  the  differentiation  between  Staphylococcus 
pyogenes  albus  and  Staphylococcus  epidermidis  albus  of  Welch  most 
difficult,  because  the  line  of  demarcation  between  the  two  is  not  a 
sharp  one  and  many  cultures  partake  of  the  features  of  both. 

Next  to  their  behavior  in  gelatine  and  milk,  the  question  of  pig- 
ment formation  is  of  distinct  value.  Cultures,  however,  must  be  al- 
lowed to  grow  for  at  least  a  week  or  two*  before  color  observation 
becomes  trustworthy.  Some  cultures  descend  from  generation  to 
generation  with  fixed  morphological  characters  and  when  such  a  cul- 
ture is  found,  the  morphology  becomes  of  aid  in  the  proper  classifica- 
tion of  the  species. 


RESEARCH    STUDIES    IN    PSORIASIS  15 

We  have  studied  24  cases  of  psoriasis,  isolating  57  cultures,  rep- 
resenting 16  different  species,  according  to  the  classification  of  the 
cocci  which  we  have  been  led  to  adopt.  Among  these  were  7  different 
cultures  of  bacilli.  All  of  these,  with  the  possible  exception  of  Ba- 
cillus pseudo-diphtheria,  do  not  in  all  probability  belong  to  the  skin 
as  their  natural  habitat,  but  represent  contamination  from  air  and 
water. 

METHOD  OF  STUDY. — Scales  were  removed  from  psoriatic  lesions 
before  and  after  preliminary  cleansing  and  planted  direct  in  the 
water  of  condensation,  in  tubes  of  slanted  1%  glucose  neutral  agar- 
agar.  After  various  trials  we  have  finally  decided  that  this  was  the 
best  method  of  obtaining  primary  growths.  All  skin  cocci  grow  more 
readily  with  glucose  than  in  plain  media. 

The  primary  cultures  are  then  incubated  for  48  to  72  hours,  be- 
cause many  cultures  are  practically  sterile  at  the  end  of  24  hours 
incubating  and  the  mixed  culture  in  the  bottom  of  the  tube  is  plated 
in  glucose  agar  and  in  gelatin.  After  further  incubation  for  48  to 
72  hours,  the  various  colonies  are  studied  and  transplanted.  After 
transplants  have  proven  to  be  in  pure  cultures,  as  far  as  can  be  deter- 
mined by  morphological  characters  of  the  organisms,  the  culture  is 
transplanted  to  the  ordinary  culture  media  generally  used  for  the 
study  of  bacteria.  In  the  process  of  classification  we  have  used  the 
nomenclature  and  technique  as  outlined  by  the  Association  of  Ameri- 
can Bacteriologists,  each  culture  being  recorded  on  a  special  Asso- 
ciation Identification  card. 

CLASSIFICATION  OF  SKIN  Cocci. 

As  already  stated,  the  available  literature  on  the  bacteriology  of 
the  skin  is  quite  meagre.  We  have  adopted  the  following  classifica- 
tion of  the  cocci  found  in  psoriasis  lesions  and  which  may  be  applied 
to  the  skin  in  general,  the  classification  being  based  principally  upon 
the  following  characters : 

1.  Liquefaction  or  non-liquefaction  of  plain  gelatine  culture  grown 

at  room  temperature  for  2  weeks. 

2.  Coagulation  or  non-coagulation  of  milk  cultures  grown  in  incu- 

bator for  5  days  ;  also  acid  and  alkali  production ;  whey  forma- 
tion ;  peptonization,  etc. 

3.  Pigment  formation  after  cultures  have  been  grown  on  agar  for 

at  least  10  days. 

4.  Morphological  characters  such  as  are  transmitted  in  at  least  2 

subcultures. 


16       SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

1.  Round  or  coccus-shaped  organisms;  growing  in  irregular  masses. 

1.  Liquefy  gelatine  slowly;  coagulate  milk  tardily;  no  pig- 

ment: 

(a)    Staphylococcus   epidermidis   albus   of  Welch.     In- 
cludes the  staphylococcus  pyogenes  albus. 

2.  Does  not  liguify  gelatine;  produces  a  yellow  pigment: 

(a)   Micrococcus  cereus  flavus. 

2.  Cocci  which  apparently  divide  in  one  plane,  with  more  or  less 

distinct  gonococcoid  shape. 

1.  Does  not  liquefy  gelatine;  does  not  coagulate  milk;  pro- 

duces no  pigment,  or  cultures  may  become  very 
slightly  yellowish  after  prolonged   cultivation: 
(a)   Diplococcus  albicans  tardus.     Includes  the  Diplo- 
coccus  albicans  tardissimus. 

2.  Does  not  liquefy  gelatine;  milk  promptly  coagulated;  pro- 

duces no  pigment: 
(a)   Diplococcus  X. 

3.  Liquifies  gelatine;  does  not  coagulate  milk;  produces  no 

pigment : 

(a)   Diplococcus  albus  liquefaciens.  Includes  the  Micro- 
coccus  albus  liquefaciens. 

4.  Liquefies   gelatine;  does  not   coagulate  milk;  produces   a 

citron  yellow  pigment : 
(a)   Diplococcus  citreus  liquefaciens. 

5.  Liquefies  gelatine ;  does  not  coagulate  milk ;  produces  a  deep 

golden  yellow  pigment: 

(a)   Diplococcus  flavus  liquefaciens.     Includes  the  Mi- 
crococcus flavus  liquefaciens. 

6.  Liquefies  gelatine;  does   not  coagulate  milk;  produces  a 

pinkish  color: 
(a)   Diplococcus  roseus. 

Diplococcus  X.  This  organism  which  has  particularly  interested 
us,  was  found  in  5  cases.  The  diplococci  are  irregular  in  shape, 
sometimes  in  fresh  cultures  the  line  of  cleavage  is  quite  distinct ;  in 
older  cultures  they  are  oval  and  may  occur  singly,  in  pairs  or  in 
threes ;  this  organism  is  Gram  positive.  It  liquefies  gelatine  in  5  to 
7  days  and  causes  prompt  coagulation  of  milk.  It  grows  very 
slowly,  very  feebly,  but  best  on  media  containing  glucose.  Pigment 
is  not  produced,  although  one  old  culture  has  shown  a  slight  yellowish 
tint  in  the  water  of  condensation.  The  colonies  in  agar  and  gelatine 
may  be  round  or  oval ;  their  margins  are  sharp  and  well  defined.  It 
grows  very  feebly  on  potato  and  bouillon.  So  far  we  have  not  been 
able  to  classify  this  organism. 


RESEARCH    STUDIES    IN    PSORIASIS  17 


CULTURES  ISOLATED  FROM  PSORIASIS  LESIONS. 

Of  (the)  24  cases  studied,  57  cultures  were  isolated,  representing 
10  different  species  of  cocci  and  6  of  bacilli,  as  follows: 

CULTURES 
Staphylococcus  epidermidis  albus  (5  of  these  pyogenes 

albus) 22 

Micrococcus  cereus  flavus 1 

Micrococcus  tetragenes 1 

Micrococcus  cinnabareus  I 1 

Diplococcus  albicans  tardus 6 

Diplococcus  (unknown  diplococcus  X)    5 

Diplococcus  albus  liquefaciens .  .  . 3 

Diplococcus  citreus  liquefaciens 1 

Diplococcus  flavus  liquefaciens »  5 

Diplococcus  roseus 3 

Bacillus  caudatum 1 

Bacillus  citreus 1 

Bacillus  nubilum 1 

Bacillus   rubium 1 

Bacillus  pseudo-diphtheria 2 

Bacillus  subtilis 3 

STAPHYLOCOCCUS  PYOGENES  AND  STAPHYLOCOCCUS  EPIDERMIDIS 

ALBUS. 

Of  considerable  interest  in  this  study  was  the  attempted  differen- 
tiation between  Staphylococcus  pyogenes  albus  and  Staphylococcus 
epidermidis  albus  of  Welch.  From  the  practical  standpoint,  this  is 
not  so  difficult  when  working  with  a  culture  isolated  from  a  stitch 
abscess  or  acne  pustule  on  one  hand  and  with  a  culture  isolated  from 
the  skin  on  the  other,  because  the  culture  from  the  abscess  will  liquefy 
gelatine  and  coagulate  milk  sufficiently  prompt  to  differentiate  it 
from  the  skin  coccus.  But  when  working  with  cultures  from  psor- 
iasis lesions,  it  is  found  that  they  vary  so  much  and  shade  one  into  the 
other,  that  differentiation  is  impossible  and  one  is  forced  to  classify 
arbitrarily  as  Staphylococcus  pyogenes  albus  or  epidermidis  albus. 

In  an  attempt  to  diffenentiate  still  further  between  these  cocci, 
we  have  tried  their  fermentative  powers  with  various  sugars  in  litmus 
agar  and  neutral  red  bouillon.  As  will  be  seen  in  the  following  table, 
the  results  were  inconsistent  and  so  similar  that  differentiation  by 
this  means  is  not  possible. 


18       SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 


TABLE   I. 

ACID  PRODUCTION  WITH  VARIOUS  SUOABB  BT  STAPHYLOCOCCUS  PYOOENES  ALBUS  AND 
STAPHYLOCOCCUS  EPIDEBMIDIS  ALBUS  (WELCH). 


Name. 
Staph.   Pyogenes  Albus. 


NEUTBAL   BED   BOUILLON. 

Dex-        Sac-       Lac-        Mai-        Dex-       Man- 
trose.     charine.      tose.         tose.         trin.         nite. 


Staph.  Epidermidis  Albus. 


+ 


TABLE   II. 

ACID  PRODUCTION  WITH  VABIOUS  SUOAHS  BY  STAPHYIX>COCCUS  PYOOEKEB  ALBTTB  AND 
STAPHYI/>COCCUS  EPIDEBMIDIS  Atsus  (WELCH). 


Name. 
Staph.  Pyogenes  Albus 


LITMUS    AGAR. 

Dex-        Sac-         Lac- 
charine.      tose. 


Mal- 
tose. 


Dex-      Man- 
trin.         nite. 


Staph.  Epid  rmidis  Albus  .....  +  + 


These  results  along  with  the  behavior  of  the  brganisms  in  gela- 
tine and  milk  indicate  their  close  relationship,  and  for  these  reasons 
we  have  classified  both  as  found  on  the  skin,  under  the  heading  of 
one  species. 

A  similar  study  was  applied  to  a  few  cultures  of  the  diplococci. 
With  these,  however,  differentiation  is  not  so  difficult  according  to 
pigment  formation,  growth  in  gelatine  and  in  milk.  It  will  be  noted 
in  the  following  tables  that  the  reduction  of  neutral  red  bouillon 


RESEARCH    STUDIES    IN    PSORIASIS  19 

differed  appreciably  with  different  species,  although  such  differentia- 
tion was  not  so  well  marked  in  litmus  agar. 

TABLE    III. 

ACID  PRODUCTION  WITH  VAHIOUS  SUGARS  BY  SKIN  DIPLOCOCCI. 
NEUTRAL.  RED  BOUILLON. 

Dex-        Sac-  Lac-        Mai-        Dex-       Man- 
Name,                                  trose.    charine.  tose.         tose.         trin.        nite. 

Diplo.   albus  liquefac — •  +             — 

Diplo.   albus  liquefac —  ± 

Diplo.  albicans  tardus +            +  +            — 

Diplo.  albicans  tardus +             +  ± 

Diplo.   flavus    liquefac —  + 

Diplo.    flavus    liquefac —  +             ± 

Diplo.    flavus    liquefac —  +             ± 

Mic.  cerus  flavus +  + 

Mic.  tetragenes    +  + 

Diplo.  roseus   — 

Diplococcus  X    +  ± 

Diplococcus  X    ±            —  — 

TABLE  IV. 
ACID  PRODUCTION  WITH  VARIOUS  SUGARS  BY  SKIN  DIPLOCOCCI. 

LITMUS  AGAR. 

Dex-        Sac-  Lac-        Mai-       Dex-        Man- 

'                               trose.    charine.-  tose.         tose.        trin.        nite. 

Diplo.  albus  liquefac +            +  +            +            + 

Diplo.   albus  liquefac —             +  — t           + 

Diplo.  albicans  tardus +            +  + 

Diplo.  albicans  tardus +            +  + 

Diplo.    flavus    liquefac —             +  ±            —            — 

Diplo.    flavus    liquefac —  ± 

Diplo.    flavus    liquefac —            +  -f-                           — 

Mic.  cerus  flavus —             +  ±            —            — 

Mic.  tetragenes   —             +  +                            — 

Diplo.  roseus   —            -f-  — 

Diplococcus   X    —  -f-                            — 

Diplococcus   X    —             ±  ±             —            — 

It  is  highly  probable  that  these  various  cocci  and  diplococci  are 
examples  of  "mutation,"  being  derived  from  an  original  parent,  but 
acquiring  certain  zymogenic  and  pathogenic  properties  as  a  result  of 
environment,  which  they  are  able  to  transmit  from  generation  to 
generation. 

ANAEROBIC  CULTURES. 

As  aerobic  cultures  failed  to  show  the  presence  of  any  unusual 
organism  in  psoriasis,  with  the  possible  exception  of  the  Diplococcus 
X,  anaerobic  cultures  were  made  in  nine  cases. 


20       SCHAMHKIU;,  KOLMKR,  HIXGKR,  AND  HAIZISS 


The  media  used  included  plain  and  glucose  agar-agar  and  bouil- 
lon ;  ascites  kidney  agar  and  ascites  kidney  serum  bouillon  as  devised 
by  Noguchi  for  the  cultivation  of  Treponema  pallidum. 

The  pyrogallic  acid  method  of  reduction  of  oxygen  and  the  use 
of  paraffine  oil  were  the  principal  methods  used  with  the  tube  cul- 
tures.   

Scales,  serum  from  the  lesions  after  removal  of  the  scales  and 
after  blistering  with  cantharides,  and  small  pieces  of  the  lesions  them- 
selves, removed  under  ethyl  chloride  anaesthesia,  were  planted  in  the 
various  media  and  examined  at  various  intervals  by  the  ordinary 
staining  methods  and  with  the  ultra  microscope.  The  following 
table  gives  the  results.  The  cocci  and  diplocci  belonged  to  the  spe- 
cies already  mentioned.  Many  cultures  were  grown  for  periods  of 
time  reaching  four  months,  but  in  no  instance  were  organisms  found 
which  could  be  regarded  as  unusual  or  especially  noteworthy. 

TABLE  V. 
ANAEROBIC  CULTURES  OF  PSORIASIS. 


Name. 

Medium. 

Result. 

Date  of 
inocu- 
lation 

B  m.     Scales    and 
serum    

Ascites     kidney     agar     and 
horse  serum  bouillon;  glu- 
cose agar  

Staphyl.  diplococci. 

1-24-13 

B  m.     Lesion  .... 

Ascftes  kidney  agar;  ascites 
kidney  bouillon  

Cocci. 

2-6-13 

j^I(«  m.    Lesion  .  .  . 

Ascites   kidney   agar;    plain 
bouillon;  plain  agar  

Cocci;  diplococci. 

2-11-13 

M  n.     Scales    and 

Ascites   agar;    serum    bouil- 
lon; glucose  agar  

Cocci;  diplococci. 

1-24-13 

L        c.    Scales  
R—  —  k.     Scales    and 

Ascites     kidney     agar     and 
serum  kidney  bouillon  
Ascites     kidney     agar     and 
serum  kidney  bouillon 

Cocci;  diplococci. 
Cocci;  diplococci. 

2-6-13 
1-21-13 

B  m.     Lesions  .  .  . 

Ascites    kidney     agar     and 
plain  agar;    glucose  agar; 
glucose  bouillon  

Cocci;  slender  bac. 

4-5-13 

B  in.       Emulsion 

Ascites  kidney  agar;  serum 
kidney  bouillon  ....         . 

Cocci;  slender  bac. 

4-5-13 

L        e.     Lesion  ;     se- 
rum   of   blister; 
scales 

Ascites  plain  agar;    glucose 

m..r;ip 

4-8-13 

B  m.    Lesion;    se- 
rum   of    blister; 
scales    

Ascites  plain  agar;    glucose 
a  trar    . 

Sterile. 

1-28-13 

N  w.      lesion  ;    se- 
rum   of    blister; 
scales   

Ascites  plain  agar;    glucose 
asrar 

Sterile. 

RESULTS  WITH  EXPERIMENTAL  CULTURE  MEDIA. 

With  the  assumption  that  an  organism  might  be  present  in 
psoriatic  lesions  which  would  grow  only  in  the  presence  of  a  peculiar 
medium,  i.e.,  with  the  products  of  metabolism  incident  to  the  infec- 
tion, various  culture  media  were  prepared  of  the  scales  of  psoriasis 
and  used  in  culturing  lesions. 

(a)  Scale  infusion:  40  grams  of  scales;  5  grains  sodium  chlor- 

ide; 1000  cc.  water.     Boiled  for  one  hour;  strained, 
cooled;  titrated  and  made  neutral  to  phenolphthalein. 

(b)  Scale  infusion:  same  as  (a)  plus  10  grams  of  Witte's  pep- 

tone. 

(c)  Scale  infusion:  same  as  (a)  and  (b)  plus  \%  glucose. 

(d)  Scale  agar:  same  as  (a)  and  (b)  plus  2%  agar-agar. 

(e)  Glucose  scale  agar:  same  as  (c)  plus  2%  agar-agar. 

(f)  Culture  media  containing  the  amino-acids  after  digestion  of 

the  proteids  by  means  of  tryspin,  were  likewise  tried 
with  a  number  of  cases. 

(g)  The  blood  serum  of  an  active  case  of  psoriasis  was  likewise 

used  as  in  the  following: 

1.  Serum  bouillon:  serum  one  part;  bouillon  two  parts. 

2.  Serum  glucose  bouillon  in  same  proportions. 

3.  Serum  glucose  agar. 

4.  Serum  kidney  agar. 

These  media  were  used  in  culturing  two  excised  psoriatic  lesions, 
but  in  neither  case  were  organisms  found  not  already  isolated  from 
other  cases. 

RESULTS. — When  these  various  media  were  used  for  isolation  or 
primary  growth  of  cultures,  it  was  found  that  cultures  grew  poorly 
on  the  peptoneless  media,  but  the  ultimate  result  and  likewise  the 
results  in  general  with  the  remaining  media  were  entirely  similar 
to  those  obtained  with  the  other  well-known  culture  media. 

MOIST  CHAMBER  CULTIVATIONS. 

Early  in  the  research  this  method  of  study  was  employed  and 
a  diplococcus  was  found  with  such'  constancy  that  we  thought  it 
might  bear  an  astiological  relationship  to  psoriasis.  Upon  isolation 
and  study  of  these  diplococci  it  was  found  that  they  belonged  for  the 
most  part,  to  the  group  described  by  Unna  and  Tommasoli.  But 
their  presence  was  so  constant  as  to  attract  for  a  time  our  attention, 
especially  so  when  controlled  by  preparations  of  other  and  similar 
cutaneous  lesions. 


22       SCHAMBKRG,  KOLMER,  RINGER,  AND  RAIZISS 

METHOD. — This  consisted  in  planting  a  small  scale  upon  a  sterile 
slide  in  a  drop  of  sterile  salt  solution  or  glucose  bouillon,  covering  it 
with  a  sterilized  cover  slip  and  partially  sealing  with  paraffine.  The 
slide  was  then  placed  in  an  improvised  Plaut  moist  chamber,  which 
is  so  designed  that  slides  are  placed  over  a  small  amount  of  water 
held  in  a  shallow  depression  of  the  dish.  In  this  way  the  preparation 
is  kept  in  a  constantly  moist  atmosphere.  We  grew  our  prepara- 
tions both  in  the  incubator  and  at  room  temperature. 

In  all,  eleven  cases  of  psoriasis  were  so  studied.  All  yielded  a 
growth  after  three  or  four  days'  incubation,  except  in  one  case. 
Groups  of  diplococci  were  found  clustered  about  the  epithelial  cells. 
In  no  instance  were  bacilli  found. 

Seven  controls  were  likewise  cultured;  two  cases  of  seborrhoeic 
dermatitis ;  three  cases  of  squamous  eczema ;  a  case  of  lupus  erythe- 
matosus  and  one  case  of  pityriasis  rosea.  All  yielded  cultures  of 
staphylococci  except  in  two  cases  of  squamous  eczema,  in  which 
staphylococci  and  Bacillus  subtilis  were  found  and  in  the  case  of 
pityriasis  rosea,  in  which  a  diptheria-like  bacillus  was  obtained. 

RESEARCHES  WITH  THE  ULTEAMICROSCOPE. 

With  the  idea  that  the  ultramicroscope  might  show  the  presence 
of  an  organism  not  readily  stained  and  not  growing  artificially,  we 
have  studied  the  serum  from  lesions  of  a  large  number  of  patients 
suffering  with  psoriasis  and  various  other  skin  diseases. 

METHOD. — After  cleansing  an  area  with  xylol  and  alcohol,  the 
superficial  layers  of  epidermis  were  removed  by  means  of  a  special 
scarifier  down  to  the  corium,  endeavoring  to  produce  the  least  pos- 
sible amount  of  bleeding.  A  drop  of  sterile  solution  was  then  placed 
upon  a  cleansed  slide  and  some  of  the  serum  secretion  from  the  de- 
nuded lesion  added  and  mixed.  A  cover  slide  was  then  adjusted  and 
the  preparation  examined. 

RESULTS. — The  first  patient  so  studied  had  an  extensive  eruption 
with  well-defined  margins  to  the  lesions.  Preparations  showed  from 
3  to  6  slender,  actively  motile  bacillary  bodies,  about  !/4  micron  in 
diameter  and  from  8  to  16  microns  in  length.  Repeated  examina- 
tions of  this  patient  showed  similar  organisms. 

In  all,  19  cases  of  psoriasis  have  been  examined  and  these 
bacillary  bodies  found  in  all  but  two.  Prolonged  search  is  sometimes 
necessary  to  discover  these  bodies,  especially  in  mild  cases. 

In  addition  to  the  above  form  of  parasite,  a  shorter,  thicker  and 
less  actively  motile  form  was  sometimes  seen.  In  some  instances, 
these  bacillary  bodies  have  a  beaded  appearance. 


RESEARCH    STUDIES    IN    PSORIASIS  23 

We  have  examined  fresh  blood  by  this  method,  to  determine 
whether  the  bodies  found  were  composed  of  fibrin.  Fibrin  is  de- 
posited later,  after  the  preparation  is  at  least  15  to  30  minutes  or 
an  hour  old.  The  filaments  are  quite  fine,  usually  attached  to  the 
corpuscles,  are  less  motile  and  may  be  of  considerable  length. 

The  following  diseases  other  than  psoriasis  were  examined  in  like 
manner  for  the  presence  of  these  bodies : 

Seborrhoeic  dermatitis ;  8  cases ;  similar  bodies  were  found  in  1  case. 

Acne  rosacea ;  1  case ;  negative. 

Squamous  eczema ;  4  cases ;  negative  in  all  but  one. 

Lichen  planus ;  1  case ;  negative. 

Dysidrosis ;  1  case ;  negative. 

Tinea  circinata ;  1  case ;  negative. 

Scabies  ;  1  case ;  negative. 

Syphilis,  tertiary;  1  case;  positive. 

Of  these  18  cases,  all  were  negative  except  three.  The  prepara- 
tions were  made  in  exactly  the  same  manner  in  all;  the  chances  for 
the  formation  of  fibrin  were  equal ;  no  claim  of  specific  pathogenicity 
is  warranted  for  these  bodies  at  the  present  time;  their  constancy 
in  psoriasis  and  their  rarity  in  the  other  dermatoses  examined,  war- 
rants us,  we  believe,  in  placing  the  observation  on  record. 

BLOOD  CULTURES  IN  PSORIASIS. 

Blood  cultures  were  made  of  10  cases.  Most  of  these  were  acute 
and  extensive  cases  and  were  cultured  during  the  developmental  stage 
of  the  eruption,  with  the  purpose  of  determining  if  an  organism 
could  be  isolated  from  the  blood  stream,  that  was  responsible  for  the 
development  of  new  lesions. 

METHOD. — An  all  glass  Burroughs  and  Welcome  syringe  was 
thoroughly  sterilized  and  from  3  to  5  cc.  of  blood  was  removed  by 
puncture  of  the  median  cephalic  vein  at  the  elbow  under  all  aseptic 
precautions  and  after  thorough  sterilization  of  the  skin.  Blood  was 
then  planted  directly  in  flasks  of  culture  media  and  grown  for  at 
least  ten  days,  with  frequent  subinoculations  and  examinations  for 
bacterial  growth.  Plain  glucose  bouillon ;  plain  and  glucose  serum 
and  ascites  bouillon  and  ascites  kidney  bouillon  were  employed. 

RESULTS. — As  will  be  seen  in  the  accompanying  table,  the  results 
were  negative  with  two  exceptions.  In  one  case  we  found  in  pure 
culture  the  unknown  Diplococcus  X  and  in  another  a  short,  solid, 
Gram  positive  bacillus,  later  identified  as  Bacillus  pseudo-diphtheria. 
Many  cases  had  dense  lesions  about  the  elbow,  so  that  it  may  have 


24       SCHAMBKHC;,  KOLMKR,  RINGKR,  AND  RAIZISS 

been  impossible  to  avoid  contamination  with  the  deeper  layers  of  the 
epiderm.  In  general,  therefore,  blood  cultures  have  not  so  far  re- 
vealed to  us  the  presence  of  a  bactersemia  in  psoriasis,  either  causa- 
tive or  secondary. 

TABLE    VI. 
BIOOD   CULTURES   IN    PSORIASIS. 

Name.  Date.  Result 

L e    1-11-13  Sterile 

N n 1-24-13  Diplococcus  X 

B m    1-26-13  Sterile 

L f    1-28-13  Sterile 

9-22-12  Pseudo-diphtheria  bacillus 

2-3-13  Sterile 

3-24-13  Sterile 

4-17-13  Sterile 

(in  hosp.  at  present)  4-4-13  Sterile 

(in  hosp.  at  present)  5-4-13  Sterile 

BLISTER  SEEUM. 

By  means  of  raising  a  blister  over  a  psoriastic  patch  with  can- 
tharidal  collodion,  serum  was  secured  which,  as  it  were,  filtered  di- 
rectly through  the  involved  area  of  skin.  Blisters  of  the  size  of  a 
silver  dollar  were  raised  quite  readily  in  active  cases  of  psoriasis 
and  the  serum  then  cultured, v  examined  with  the  ultra  microscope 
and  stained  preparations  examined  for  the  bodies  described  by  Lip- 
schutz. 

JErobic  and  anaerobic  cultures  in  plain  and  glucose  agar,  plain 
and  glucose  bouillon,  ascites  bouillon  and  agar  and  ascites  kidney 
bouillon  and  agar,  yielded  sterile  cultures.  These  results  were  some- 
what surprising,  as  no  effort  was  made  to  cleanse  the  patch  before 
applying  the  blistering  collodion. 

Examination  by  means  of  the  ultramicroscope  showed  the  de- 
velopment of  fibrils  of  fibrin  but  nothing  else  worthy  of  mention. 

BACTERIAL  VACCINES  (BACTERINS)  ix  PSORIASIS. 

Having  isolated  a  number  of  different  species  of  organisms  from 
psoriatic  lesions,  we  considered  the  advisability  of  preparing  and  ad- 
ministering a  vaccine.  The  supposedly  common  skin  organisms 
may  represent  the  cause  as  operative  under  special  metabolic  condi- 
tions and,  therefore,  their  vaccine  may  show  this  relationship  and 
be  of  some  therapeutic  value. 

Two  different  vaccines  were  prepared  of  pure  cultures  of  organ- 
isms recovered  from  psoriasis  lesions.  The  first,  prepared  on  No- 


RESEARCH    STUDIES    IN    PSORIASIS  25 

vember  4th,  consisted  of  6  different  cultures  of  diplococci  from  6 
different  cases.     The  organisms  were  as  follows: 

Diplo-tardus  albicans. 
Diplo-albus  liquefaciens. 
Diplo-flavus  liquefaciens. 
Unknown  diplococci  (X). 
Diplo-citreus  liquefaciens. 

The  second  vaccine  was  prepared  on  Feb.  19,  1913,  of  24  cultures 
including  : 

Diplo-tardus  albicans. 
Diplo-flavus  liquefaciens. 
Diplo-citreus  liquefaciens. 
Three  unknown  diplococci  (X). 
Micrococcus  cereus  flavus. 
Micrococcus  tetragenes. 
Micrococcus  flavus. 
Bacillus  pseudo-diphtheria. 
Bacillus  ferrugineum. 
Bacillus  subtilis. 
Unknown  coccus. 

The  vaccines  were  prepared  in  the  usual  manner,  sterilization 
being  effected  by  heating  to  58°  C.  for  one  hour.  The  dose  was  from 
3  to  5  hundred  million  cocci. 

RESULTS. — A  number  of  psoriasis  patients  were  treated  with  the 
above  vaccines,  but  the  results  were  indifferent  and  inconclusive. 

While  negative  results  are  not  conclusive,  yet  the  failure  of  vac- 
cines to  aid  in  this  chronic  affection,  combined  with  the  negative 
results  of  complement-fixation  reactions  to  detect  the  presence  of  an 
antibody  for  these  organisms  in  the  nature  of  an  amboceptor,  is  evi- 
dence against  their  being  active  participants  in  the  cause  of  psoriasis. 

INOCULATION  EXPERIMENTS. 

The  successful  inoculation  of  the  lower  animals  with  psoriasis 
would  facilitate  research  to  a  marked  degree  and  above  all  would 
afford  more  conclusive  evidence  regarding  the  nature  of  the  disease. 

Accordingly  we  have  made  several  attempts  during  the  past  year 
to  infect  the  Macacus  rhesus  with  psoriasis,  using  scales,  serum,  im- 
plantation with  actual  buttons  of  psoriatic  skin  and  Jntraperitoneal 
injection  of  defibrinated  blood  of  an  active  case  of  psoriasis. 

The  method  of  skin  implantation  was  especially  hopeful  of  posi- 
tive results  if  a  parasite  were  the  cause  of  psoriasis,  because  under 
the  conditions  of  the  experiment  the  infectious  agent  was  certainly 


26       SCHAMBERG,  KOLMER,  RIXGER,  AND  RAIZISS 

transplanted,  the  only  question  being  the  subsequent  vitality  of  the 
"button"  and  the  question  of  proper  soil. 

Having  found  that  cases  of  psoriasis  were  likely  to  improve  under 
a  low  protein  diet  or,  conversely,  were  apt  to  grow  worse  under  a 
high  protein  diet,  we  kept  a  monkey  on  a  diet  of  milk,  plasmon  and 
peanuts  for  two  weeks  until  2  gin.  of  nitrogen  were  being  eliminated 
in  24  hours.  A  "button"  of  psoriatic  skin  was  then  implanted,  which 
healed  readily,  but  did  not  show  any  evidence  of  having  transmitted 
psoriasis  three  months  after  the  inoculation. 

Brief  protocols  of  these  experiments  are  as  follows: 

Experiment  1,  Jan.  4,  1913.  Monkey.  Macacos  rhesus.  Area 
on  back  shaved  and  cleansed ;  skin  abraded  and  inoculated  with 
bloody  scrum  removed  from  beneath  the  scales  of  a  well-marked  case 
of  psoriasis.  Result:  abrasions  healed;  no  resultant  eruption. 

Experiment  2,  Jan  6,  1918.  Monkey.  Macacus  rhesus.  Area 
on  back  shaved  and  cleansed.  Under  ethyl  chloride  spray,  a  button 
of  skin  about  6  mm.  in  width  was  removed  with  a  Keyes'  skin  punch. 
A  similarly  sized  button  was  removed  from  the  margin  of  a  well- 
marked  patch  of  psoriasis  and  implanted  in  the  monkey.  A  simple 
protective  dressing  was  applied.  Result :  the  skin  implantation  was 
successful  and  healing  occurred  without  infection,  but  there  was  no 
evidence  of  psoriasis  resulting. 

Experiment  3,  Jan.  22,  1913.  Monkey.  Macacus  rhesus.  Area 
on  back  shaved  and  cleansed  and  then  lightly  scarified  as  in  the 
operation  of  vaccination.  Secretions  and  scales  from  a  lesion  of 
psoriasis  were  then  rubbed  in  quite  thoroughly.  Result :  healing ;  no 
evidence  of  psoriasis. 

Experiment  4,  April  4,  1913.  Monkey.  Macacus  rhesus.  Kept 
on  a  diet  of  milk,  plasmon  and  peanuts  for  two  weeks.  Was  elim- 
inating in  urine,  according  to  an  analysis,  2  gm.  of  nitrogen  in  24 
hours.  Area  of  back  prepared  and  implanted  with  a  button  of 
skin  removed  from  a  psoriasis  plaque.  Animal  kept  on  same  diet. 
Result:  too  early  for  definite  opinion,  but  probably  negative. 

Experiment  5,  May  27,  1913.  Monkey.  Macacus  rhesus.  Re- 
ceived an  intraperitoneal  injection  of  6  cc.  of  defibrinated  blood  re- 
moved from  a  case  of  psoriasis.  The  animal  showed  no  ill-effects 
and  up  to  five  weeks  later,  had  shown  no  evidences  of  psoriasis. 
General  health  excellent. 

While  it  is  .necessary  to  wait  even  a  longer  period  of  time  before 
a  negative  result  can  be  recorded  for  some  of  these  experiments,  yet 
as  they  are,  they  indicate  quite  conclusively  the  difficulty  of  trans- 
mitting this  disease  (further  experiments  in  inoculation  will  be  made 
in  the  near  future). 


RESEARCH    STUDIES    IN    PSORIASIS  27 

SUMMARY. 

1.  Nine  of  48  cases  of  psoriasis,  18.7%  yielded  positive  Wasser- 
mann  reactions,  using  an  alcoholic  extract  of  luetic  liver  as  antigen. 
With  antigens  of  cholesternized  alcoholic  extracts  of  human  and  beef 
heart,  over  28%   of  22  cases  reacted  positively.     From  a  clinical 
study  of  the  patients  whose  serums  were  studied,  the  positive  tests 
cannot  all  be  attributed  to  syphilis,  although  this  might  be  true  of  a 
few  of  them ;  on  the  other  hand,  some  significance  must  be  attached 
to  them,  which  future  research  alone  can  reveal. 

2.  Using  for  antigens  aqueous  and  alcoholic  extracts  of  psoriasis 
scales  and  of  a  large  number  of  cultures  of  organisms  isolated  from 
lesions,  complement  fixation  was  not  found  to  occur  with  10  sera  from 
active  cases  of  psoriasis.     These  results  would  indicate  that  either 
the  true  antigen  was  not  present  in  the  extracts  of  scales  and  cul- 
tures used,  or  that  the  psoriasis  antibody,  if  it  exists,  was  not  present 
in  the  sera  in  sufficient  amount  to  inactivate  complement  with  the 
extracts  used  in  this  study. 

3.  Sixteen  different   organisms  were  isolated   from   57   cultures 
from  24  cases  of  psoriasis.     No  organism  was  found  which  could  be 
regarded  as  bearing  an  aetiological  relationship  to  the  disease. 

4.  An   unidentified  diplococcus   "X"  was   found  in   5   psoriatic 
lesions  and  in  1  blood  culture  and  is  deserving  of  further  study. 

5.  The  use  of  anaerobic  methods  and  special  culture  media,  com- 
posed of  the  scales  and  secretions  of  psoriasis,  did  not  show  the  pres- 
ence of  any  special  parasite. 

6.  Numerous  growths   of  scales  in  moist  chambers  showed  the 
presence  of  diplococci,  but  no  unusual  organism  or  fungus. 

7.  Investigation  with  the  ultramicroscope  discovered  the  pres- 
ence of  a  motile  bacillary  body  in  17  out  of  19  cases  of  psoriasis.     In 
18  other  dermatoses  these  were  found  in  3  instances.     These  bodies 
are  being  further  studied. 

8.  Cultures  and  microscopical  examinations  of  fluid  secured  by 
blister  over  psoriasis  lesions,  yielded  negative  results. 

9.  Vaccine  treatment  carried  out  with  vaccines  made  from  a  large 
number  of  different  species  of  organisms  found  in  psoriasis  lesions, 
yielded  indifferent  and  inconclusive  results. 

10.  Inoculation  experiments  on  monkeys,  including  the  implanta- 
tion of  buttons  of  psoriasis  skin,  scales,  serum  and  defibrinated  blood, 
were  negative  in  one  to  six  months  after  inoculation. 


PROTEIN  METABOLISM  IN  PSORIASIS. 


TABLE    OF    CONTENTS. 

Earlier  Researches  in  the  Metabolism  of  Psoriatics  31 

The  Principles  of  General  Metabolism   32 

Principles  of  Protein  Metabolism 34 

The    Care    of    the    Patients    36 

Food 37 

Methods  of  Analyses 38 

Patient  No.  3 38 

Summary  of  Results  Obtained  in  the  Study  of  Patient  No.  3 47 

Patient  No.  4 69 

Summary  of  Results  Obtained  in  the  Study  of  Patient  No.  4 77 

Patient  No.  5    79 

Summary  of  Results  Obtained  in  the  Study  of  Patient  No.  5 88 

Patient  No.  8 88 

Summary  of  Results  Obtained  in  the  Study  of  Patient  No.  8 98 

Patient  No.  9  98 

Patient  No.  7 109 

Discussion  of  Results   120 

The   Value  of  the   Eliminated   Nitrogen   in  the   Interpretation   of   Processes 

of  Metabolism   121 

The  Minimal  Protein  Requirements  and  the  Minimal  Protein  Catabolism 122 

Nitrogen  Retention  125 

Nitrogen  Retention  in  Normal  Adult  Individuals 125 

Nitrogen  Retention  in  Growing  and  Convalescent  Individuals 127 

Nitrogen   Retention   in   Psoriasis    128 

Influence  of  a  Low  Protein  Diet  on  the  Course  of  Psoriasis 131 

The  Relationship  Between  Retained  Nitrogen  and  Gain  in  Body  Weight 133 

Resum£  of  the  Clinical  Results 134 

Summary  and  Conclusions 137 

Bibliography   139 


RESEARCH    STUDIES    IN    PSORIASIS  31 


EARLIER  RESEARCHES  IN  THE  METABOLISM  OF  PSORIATICS. 

THEORIES  which  hold  disturbances  of  metabolism  responsible 
for  certain  diseases  of  the  skin  can  be  traced  back  to  the  early 
history  of  dermatology.  Many  interesting  contributions  have 
been  made  by  French  authors,  presenting  theories  which  connect  va- 
rious cutaneous  affections  with  disturbances  in  uric  acid  metabolism. 
Some  of  these  views  are  held  by  certain  clinicians  at  the  present 
time.  And  yet  these  theories  have  no  experimental  foundation  and 
are  not  in  harmony  with  our  modern  knowledge  of  uric  acid  metab- 
olism. Of  course  there  cannot  be  excluded  the  possibility  that  there 
may  exist  derangements  in  the  uric  acid  metabolism  of  patients 
afflicted  with  diseases  of  the  skin  and,  ultimately,  perhaps  some  truth 
may  be  found  in  the  teachings  of  the  early  French  school.  Thus  far 
we  possess  no  facts  indicating  the  existence  of  such  derangements  and 
the  speculative  theories  about  "arthritism"  or  "uric  acid  diatheses," 
under  discussion  for  nearly  half  a  century,  still  await  experimental 
demonstration. 

In  the  last  two  decades  ^there  have  appeared  a  great  number  of 
contributions  on  the  relationship  between  disturbed  metabolism  and 
skin  diseases.  Almost  all  of  them  are  based  on  clinical  observations, 
with  an  occasional  analysis  of  the  patient's  urine.  Various  internal 
diseases  were  then  assigned  as  the  cause  of  the  skin  affection  under 
investigation.  If  an  examination  of  the  urine  showed  an  accidental 
increase  of  one  of  the  urinary  constituents,  the  cause  of  the  skin  dis- 
ease was  ascribed  to  that  particular  condition.  For  instance,  a  tem- 
porary increase  in  the  daily  output  of  urea,  or  a  temporary  de- 
crease, was  associated  with  the  causation  of  the  skin  eruptions, 
whereas  the  real  reason  for  these  changes  in  the  urea  output  was 
doubtless  the  diet ;  in  one  case  it  was  richer  in  nitrogen,  in  the  other 
case  poorer. 

In  many  instances  auto-intoxication  of  the  body  was  regarded 
as  giving  rise  to  diseases  of  the  skin  and  was  expressed  in  the  abnor- 
mal quantitative  output  of  different  organic  constituents  of  the 
urine.  In  general,  those  works  were  largely  of  a  clinical  character 
and  were  practically  worthless  as  far  as  throwing  any  real  light  on 
the  metabolism  of  skin  diseases  was  concerned. 

Recently  there  have  appeared  several  communications  dealing 
with  the  metabolism  of  psoriatics.  One  of  these  deals  with  the  nitro- 
gen and  sulphur  metabolism,1  and  seems  to  have  been  carried  out  in  a 
very  painstaking  and  accurate  manner.  The  length  of  the  ex- 


32       SCHAMBERG,  KOLMER,  RINGER,  AXIJ  RAIZISS 

jK-rinu nt,  liowcvcr,  was  too  short  to  permit  of  any  definite  conclu- 
sions. The  entire  experiment  lusted  14  days  and  was  divided  into  4 
periods,  3  of  four  days  each  and  1  of  two  days.  During  these 
periods  different  diets  were  given  containing  varying  amounts  of 
nitrogen.  These  periods,  in  our  estimation,  are  too  brief  to  permit 
of  any  definite  deductions  with  regard  to  the  nature  of  the  protein 
metabolism  in  psoriatics. 

In  inaugurating  a  research  on  the  metabolism  of  psoriatics,  it 
seemed  to  us  essential  to  study  the  protein  metabolism  first.  We  did 
this  for  several  reasons.  Firstly,  because  the  different  theories  that 
were  evolved  in  the  early  literature  of  psoriasis  centered  mainly 
around  the  question  of  disturbed  protein  catabolism.  Secondly,  be- 
cause the  study  of  protein  metabolism  lends  itself  to  very  accurate 
investigations,  because  of  the  ease  with  which  the  nitrogen  balances 
can  be  studied.  Thirdly,  because  protein  metabolism  in  the  normal 
is  most  thoroughly  understood  and  gives  us  a  fair  basis  for  com- 
parison. 

Before  presenting  the  results  of  our  experiments,  however,  we 
have  considered  it  advisable  to  briefly  review  the  general  principles 
that  govern  the  general  and  protein  metabolism  of  normal  individuals. 

THE   PRINCIPLES  OF  GENERAL  METABOLISM. 

By  metabolism,  we  understand  all  the  processes,  chemical,  physical  and  bio- 
logical, that  are  involved  in  the  utilization,  absorption  and  assimilation  of  food 
stuffs;  the  transformations  that  these  undergo  before,  during  and  after  their 
assimilation,  and  the  elaboration  and  excretion  of  all  their  end  products  (waste 
products).  All  phenomena  of  living  cells,  whether  motor,  reproductive  or  sen- 
sory, are  very  closely  associated  with  processes  of  metabolism. 

The  chemical  processes  of  metabolism  are  divided  into  two  phases: 

1.  Anabolism:  the  upbuilding  of  substances  or  tissues. 

2.  Catabolism :  the  breaking  down  of  complex  substances  into  simpler  'ones. 
All  the  foodstuffs  of  the  body,  with  the  exception  of  the  inorganic  salts,  whose 

function  it  is  to  maintain  proper  osmotic  conditions  in  the  cells  and  fluids  of  the 
body,  are  such  as  to  be  able  to  undergo  processes  of  oxidation  (combustion), 
which  processes  are  exothermic,  i.e.,  are  associated  with  the  formation  of  heat, 
The  principal  foodstuffs,  all  of  which  are  capable  of  yielding  energy,  are  divided' 
into  three  classes: 

1.  Carbohydrates. 

2.  Fats. 

3.  Proteins. 

The  carbohydrates  and  fats  have  as  their  constituents  carbon,  hydrogen  and 
oxygen,  chemically  united  in  definite  and  peculiar  forms.  In  normal  individuals 
these  two  foodstuffs  undergo  complete  oxidation.  All  the  carbon  becomes  oxi- 
dized to  carbon  dioxide  and  all  the  hydrogen  becomes  oxidized  to  water.  The 
carbon  dioxide  thus  formed  is  eliminated  mainly  through  the  respiratory  tract 
and  the  water  formed  is  eliminated  through  the  kidneys,  by  perspiration,  or  in 
the  moisture  of  the  expired  air. 

The  protein  molecule  is  composed  of  carbon,  hydrogen,  oxygen,  nitrogen  and 


RESEARCH    STUDIES    IN    PSORIASIS  33 

sulphur.  The  proteins  that  form  the  nuclear  elements  of  cells  contain  also  phos- 
phorus. It  is  at  once  evident  that  while  the  carbon  and  hydrogen  that  are  ex- 
creted as  waste  or  end  products  in  animal  metabolism  may  find  their  origin  in 
carbohydrate,  fat  or  protein,  the  nitrogen,  and  to  a  certain  extent  also  the  sulphur 
and  phosphorus,  have  only  one  source  of  origin — the  proteins.  After  the  protein 
is  catabolized  in  the  body,  the  nitrogen  is  eliminated  in  the  form  of  urea,  ammonia, 
uric  acid,  purin  and  other  bodies.  Most  of  the  nitrogenous  waste  products  are 
excreted  through  the  kidneys  and  a  small  amount  passes  out  with  the  faeces  and 
perspiration.  In  the  faeces  we  may  find  some  unresorbed  proteins  which  never 
played  a  role  in  metabolism.  We  shall  have  occasion  later  to  discuss  this  subject 
in  greater  detail. 

Since  the  average  protein  contains  about  16%  nitrogen,  we  are  enabled,  by 
determining  the  nitrogen  in  the  excreta  and  multiplying  its  value  by  6.25,  to  find 
the  amount  of  protein  that  was  catabolized  in  the  animal  organism.  Voit,  who  has 
played  the  most  important  role  in  the  framing  of  our  present  conceptions  of 
protein  metabolism,  was  the  first  to  recognize  the  relationship  between  urinary 
nitrogen  and  protein  metabolism. 

The  proteins  are  very  complicated  condensation  products  of  about  16  different" 
amino-acids  which,  in  the  process  of  digestion,  suffer  hydrolysis,  which  causes  a 
disruption  of  the  molecule  into  its  individual  component  amino-acids.* 

Each  amino-acid  has  its  own  life  history  in  intermediary  metabolism.  Here 
we  can  only  refer  to  some  of  the  works  which  deal  with  this  subject  in  greater 
detail.^  Later,  we  shall  return  to  the  subject  of  nitrogenous,  sulphur  and  phos- 
phorus end  products  of  protein  metabolism. 

HEAT  FORMATION.  Just  as  in  the  combustion  of  carbon  and  hydrogen  outside 
the  animal  body,  the  process  is  associated  with  the  formation  of  heat,  so  in  the 
animal  body,  the  combustion  of  these  substances  is  accompanied  by  the  evolution 
of  heat,  which  serves  to  maintain  the  body  temperature.  The  amount  of  heat 
produced  depends  entirely  upon  the  amount  of  material  burnt  and  the  total 
metabolism  of  the  cells  of  the  body  is  determined  by  its  requirements  for  kinetic 
energy  and  by  the  amount  of  heat  given  off  to  the  surrounding  atmosphere. 

The  heat  produced  by  an  individual  is  measured  in  terms  of  calories.  One 
calorie  is  the  equivalent  of  the  amount  of  heat  required  to  raise  one  liter  of  water 
from  0°  to  1°  C. 

The  following  amounts  of  heat  are  generated  in  the  animal  body  in  the  com- 
bustion of  one  gram  of  the  different  foodstuffs: 

Starch 4.10  calories 

Cane  sugar 3.96         " 

Glucose   3.75         " 

Animal  fat 9.3  " 

Protein    4.1  " 

The  total  amount  of  heat  produced  by  a  fasting  normal  individual,  in  a  state 
of  complete  rest,  at  a  temperature  corresponding  to  that  of  his  body  (to  prevent 
loss  of  heat  by  radiation  and  conduction)  is  called  the  "basal  heat  production." 

*  Amino-acids  are  fatty  acids  in  which  one  hydrogen  atom  of  the  alkyl  radical 
is  replaced  by  an  amino  radical  (NH2)  e.g., 

CH3— COOH   )  j  CH2— NH2— COOH 

Acetic  acid       l"  "j   Glycocoll  or  amino-acetic  acid 

CH2— COOH   -\  f  CHNH2— COOH 


CH2— COOH    f  ^  CH2— COOH 

Succinic   acid    1  (^  Aspartic  acid  or  amino-succinic  acid. 


IM       SCHAMHKKG,  KOLMKR,  RINGER,  AND  RAI/ISS 

This  represents  the  lowest  degree  of  nietabolisni  compatible  witli  life.  In  a  huinap 
individual  this  niuounts  to  about  25  calories  per  kg.  of  body  weight  per  -21  hours. 
The  normal  individual  cannot  however,  get  along  on  this  low  basis,  for  the  normal 
individual  constantly  finds  himself  in  an  atmosphere  where  the  temperature  is 
much  lower  than  that  of  his  body.  This  results  in  heat  being  constantly  lost  by 
the  body  by  radiation  and  conduction  to  the  surrounding  space.  To  maintain 
the  body  temperature,  therefore,  a  greater  amount  of  heat  has  to  be  produced 
than  is  necessary  for  the  "basal  maintenance  of  life."  From  the  aforesaid,  it  be- 
comes evident  that  to  a  very  .large  extent,  the  total  heat  production  must  have 
some  relationship  to  the  total  area  of  body  surface.  Rubner3  was  the  first  to  call 
attention  to  this.  The  details  of  this  were  worked  out  by  E.  Voit4  in  a  very 
beautiful  way.  The  results  of  his  experiments  are  here  tabulated: 

Calories. 


Species  (5)  Weight  in  kg.  Per  kg.     Per  square  meter 

of  body  surface. 

Pig    128.0  19.1  i()78 

Man    64.3  32.1  1042 

Dog    15.2  51.5  1039 

Mouse 0.018  212.0  1188 

This  table  shows  to  what  a  remarkable  extent  the  amount  of  heat  produced 
per  square  meter  of  body  surface  is  constant  for  different  animals  and  different 
sizes.  When,  however,  we  come  to  consider  the  amount  of  heat  produced  per  kg. 
of  body  weight,  we  learn  something  that  is  of  fundamental  importance,  namely, 
that  with  the  diminution  of  the  weight  of  the  individual,  there  is  a  constant 
increase  in  the  heat  production  per  kg.  of  body  weight.  This  must  always  be 
borne  in  mind  in  establishing  dietaries.  The  small  man  must  always  be  allowed 
a  larger  amount  of  food  in  proportion  to  his  weight  than  a  large  man. 

This  is  brought  out  very  clearly  in  the  researches  of  Carnerer**: 


Calories  per  Calories  per  sq.  meter 

kg.  per  day.  of  surface  per  day. 

lit  i    i  >  i 


Child,   1   month 91  1  .'.M 

Dwarf  (6  kg.  rest) 83  1231 

Child,  2  years ' 81  1231 

Child,  10  years 60  1389 

Child,  14  years 52  1452 

Adult   (average  work) . . . '. 42  1390 

PRINCIPLES  OF  PROTEIN   METABOLISM. 

If  we  feed  an.  animal  with  a  sufficient  amount  of  carbohydrates,  fats  and 
protein  and  compare  the  nitrogen  in  the  food  with  the  amount  of  nitrogen  in 
the  excreta  (urine,  faeces  and  perspiration)  and  find  that  the  two  balance,  we 
consider  the  animal  in  a  state  of  nitrogenous  equilibrium,  i.e.,  the  animal  is 
receiving  as  much  nitrogen  in  the  protein  of  its  food  as  it  is  metabolizing  and 
eliminating  in  the  excreta.  If  the  animal  is  found  to  eliminate  less  nitrogen 
than  is  ingested,  it  is  evident  that  the  animal  is  storing  nitrogenous  material. 
We  consider  the  animal  to  be  in  a  state  of  positive  nitrogen  balance.  This  state 
usually  occurs  in  the  growing  child,  in  patients  convalescent  from  a  wasting  disease 
and  in  the  athlete  in  training.  On  the  other  hand,  if  the  nitrogen  in  the  excreta 
is  found  to  be  greater  than  in  the  ingested  food,  it  is  clear  that  the  animal  is 
losing  its  own  body  protein.  We  consider  that  animal  to  be  in  a  state  of  negative 
nitrogen  balance.  This  state  usually  occurs  in  starvation,  undernutrition,  in 


RESEARCH    STUDIES    IN    PSORIASIS  35 

persons  suffering  from  wasting  diseases  like  carcinoma,  tuberculosis,  fever  and 
other  forms  of  toxaemia. 

If  the  quantity  of  protein  intake,  in  an  individual  who  maintains  nitrogenous 
equilibrium,  is  steadily  increased,  the  nitrogen  elimination  of  that  individual  will 
increase  correspondingly,  until  an  equilibrium  is  struck  on  a  higher  level.  This 
adjustment  does  not  take  place  at  once,  but  in  the  course  of  two,  three  or  some- 
times four  days.  During  this  period  of  adjustment,  a  considerable  amount  of 
nitrogen  is  retained  in  the  body.  On  the  other  hand,  if  the  nitrogen  intake  is 
diminished,  nitrogen  equilibrium  becomes  established  on  a  lower  level  with  the 
opposite  effect,  i.e.,  during  the  first  few  days  more  nitrogen  is  eliminated  than  is 
ingested  (see  page  74). 

Although  it  is  possible  to  keep  an  individual  in  nitrogenous  equilibrium  on  any 
level  up  to  the  point  of  the  maximum  digestive  and  resorptive  capacities  of  that 
individual  for  protein,  it  is  found  experimentally  that  there  is  a  low  limit  of 
protein  below  which  it  is  impossible  to  maintain  nitrogenous  equilibrium  and  below 
which  we  cannot  reduce  the  protein  metabolism.  Any  attempt  to  keep  an  indi- 
vidual on  a  protein  diet  below  that  level  will  result  in  a  negative  nitrogen  balance, 
i.e.,  a  loss  of  protein  from  the  tissues.  Ihis  low  protein  level  was  recognized  by 
Rubner"  as  the  "wear  and  tear"  quota,  which  represents  the  amount  of  protein 
that  goes  to  replace  the  nitrogenous  material  that  is  actually  broken  down  during 
the  activities  of  the  cells  in  their  life  processes. 

In  Voit's  early  researchesS  he  showed  that  nitrogenous  equilibrium  may  be 
maintained  on  a  diet  consisting  of  protein  alone.  In  this  case  very  large  quantities 
of  protein  are  catabolized,  first,  to  cover  the  "wear  and  tear"  quota  and,  second, 
to  cover  the  dynamic  requirements  of  the  body.  If  non-protein  foodstuffs,  as  car- 
bohydrates and  fats,  were  added  to  the  diet,  nitrogenous  equilibrium  was  found 
to  be  maintained  on  a  much  lower  level.  The  carbohydrates  and  fats  thus  exert 
a  sparing  influence  on  the  protein  metabolism.  The  sparing  influence  of  car- 
bohydrates on  the  protein  metabolism  in  man  was  first  demonstrated  by  Lusk 
while  working  in  Voit's  laboratory  at  Munich^. 

This  subject  was  further  studied  by  Rubner,lo  Landergren,11  Cathcarti2  and 
others,  who  have  shown  that  carbohydrates  may  even  reduce  the  starvation  re- 
quirements of  protein. 

All  these  experiments  show  very  plainly  that  within  very  wide  limits  the 
protein  metabolism  may  be  influenced  by  the  amounts  of  carbohydrates  and  pro- 
teins in  the  food.  By  various  arrangements  of  the  quantities  of  these  foodstuffs, 
it  was  shown  to  be  possible  to  maintain  nitrogenous  equilibrium  at  any  arbitrary 
level  above  the  wear  and  tear  quota.  The  question  then  naturally  presented 
itself:  What  shall  be  considered  a  physiological  amount  of  protein  in  one's  diet? 
This  question  has  absorbed  the  minds  of  a  great  many  investigators  and  a  tre- 
mendous amount  of  material,  experimental  and  statistical,  has  been  collected. 
Although  this  discussion  stimulated  the  performance  of  a  great  many  experiments 
that  revealed  to  us  the  laws  that  govern  protein  metabolism  in  health  and  disease, 
the  original  question  is  as  open  now  as  it  was  forty  years  ago  when  it  was  first 
raised. 

On  the  basis  of  a  great  many  experiments,  Voit  suggested  that  for  an  adult 
doing  a  moderate  amount  of  work,  a  diet  containing  118  grams  of  protein  (which 
contains  17.28  grams  of  nitrogen)  with  a  total  food  supply  of  30o5  calories  was 
required.  This  served  as  a  starting  point  of  one  of  the  most  heated  debates 
recorded  in  the  annals  of  physiological  literature. 

It  was  soon  recognized  that  the  great  physiological  importance  of  protein  in 
the  diet  was  due  to  its  ability  to  "repair  body  tissues,"  and  the  discussion  cen- 
tered around  the  question:  What  constitutes  a  "repair  quota"  or  "wear  and 
tear"  quota? 

Voit's  protein  quota  of  118  grams  of  protein  =  17.28  grams  of  nitrogen  for 
an  individual  of  75  kg.  of  body  weight,  allows  approximately  1.5  grams  of  protein 


3(>       SCHAMBKHG,  KOLMKK,  RINGKU,  AND  RAI/ISS 

or  0.£J  gram  of  nitrogen  JUT  kg.  of  body  weight.  A  great  many  physiologists  con- 
sidered this  excessive,  especially  since  it  was  demonstrated  that  other  races  maintain 
nitrogenous  equilibrium  on  much  lower  levels.  For  example,  it  was  shown  that 
the  Italian  laborer  does  not  consume  more  than  about  30  grams  of  protein  = 
•l.H  grams  of  nitrogen  and  that  the  Japanese  coolies  get  along  on  a  diet  of  rice 
containing  not  more  than  i?5  grams  of  protein  =  4.0  grams  of  nitrogen.13  These 
figures,  however,  must  not  be  taken  by  themselves,  but  in  relationship  to  the  aver- 
age body  weight  of  the  individual  experimented  upon.  Thus  the  average  Japanese, 
who  lives  on  a  i  gram  nitrogen  regime  weighs  about  one-half  as  much  as  the 
average  husky  Ciennan  who  lives  on  the  Voit  protein  standard.  During  the  past 
few  years,  however,  very  satisfactory  evidence  has  been  obtained  in  this  country 
and  abroad,  which  shows  that  men  who  come  from  races  which  are  habitually  large 
protein  consumers  can  maintain  for  long  periods  of  time,  their  well-being,  nitrog- 
enous equilibrium  and  body  weight,  on  just  one-half  of  the  Voit  regime.** 

In  the  discussion  of  this  problem,  a  very  interesting  series  of  observations  was 
brought  to  light  and  one  that  is  very  closely  related  to  the  main  problem  of  our 
present  paper.  These  observations  deal  with  the  influence  of  a  high  protein  diet 
on  tissue  formation  and  growth.  Mention  was  previously  made  (see  page  35)  of 
the  fact  that  in  changing  the  diet  from  one  level  to  another,  the  body  required 
several  days  to  aecomodate  itself  to  the  new  diet,  before  nitrogenous  equilibrium 
was  again  established.  In  changing  the  diet  from  a  low  to  a  high  protein  level, 
it  takes  two  or  three  days  before  the  eliminated  nitrogenous  waste  will  equal  the 
nitrogenous  intake.  During  this  period  of  adjustment,  nitrogenous  material  is 
retained  in  the  system.  The  great  important  question  is:  what  becomes  of  it? 
Is  it  retained  only  temporarily  or  does  it  become  part  of  the  body  cells?  The 
scope  of  this  question  was  further  broadened  when  it  was  shownis  that  the  protein 
metabolism  can  be  reduced  to  a  very  low  level  by  feeding  very  large  quantities 
of  carbohydrates.  It  was  found  that  if  the  protein  intake  remained  the  same  and 
the  carbohydrate  supply  was  suddenly  raised,  there  was  a  marked  diminution  in 
the  nitrogen  output  in  the  urine.  The  result  was  a  considerable  retention  of 
nitrogen  in  the  body.ifi  The  question  of  the  formation  of  "tissue"  by  the  stored 
nitrogen  now  became  vital. 

Retention  of  nitrogen  in  the  growing  individual  and  the  convalescent,  has 
long  been  recognized.  We  explain  it  by  the  generative  and  regenerative  ten- 
dencies of  living  cells.  In  the  case  of  the  former,  it  was  associated  with  growth;  in 
the  case  of  the  latter,  with  the  restorative  processes  of  the  cells.  But  it  was 
found  very  difficult  to  explain  the  significance  of  the  retention  of  nitrogen  in  a 
healthy,  well-nourished  adult.  The  problem  is  one  of  great  practical  importance 
and  briefly  stated,  is  this:  Do  we  deal  with  a  retention  of  nitrogen  that  is  deposited 
in  the  cells  of  the  body  in  an  unorganized  form  of  protein,  which  although  it  is 
stored  in  the  cells,  does  not  become  a  vital  functionating  part  of  the  cells  and  does 
not  add  to  the  cells'  efficiency  any  more  than  does  a  similar  amount  of  fat  or 
glycogen,  or  does  this  retention  of  nitrogen  mean  an  increase  in  the  living  pro- 
toplasm of  the  cells,  associated  with  increased  protoplasmic  physiological  effi- 
ciency? The  economic  importance  of  this  question  cannot  fail  to  be  appreciated. 

Since  the  results  of  our  investigation  are  very  intimately  connected  with  this 
problem,  we  shall  postpone  the  further  discussion  of  it  until  after  the  presentation 
of  our  experimental  studies. 

THE  CARE  OF  THE  PATIENTS. 

All  the  experiments  were  performed  under  the  strictest  rulings 
that  are  necessary  for  exact  metabolism  studies. 

The  patients  were  kept  in  private  rooms  at  the  Polyclinic  Hos- 
pital, which  were  located  on  the  same  floor  as  the  Laboratory.  The 


RESEARCH    STUDIES    IN    PSORIASIS  37 

patients  were  under  the  nursing  care  of  Miss  Julia  Dorsey,  whose 
valuable  cooperation  we  take  pleasure  in  acknowledging.  In  each 
room  there  was  a  set  of  utensils  for  the  quantitative  collection  of 
the  urine  and  faeces.  The  urine  was  preserved  with  toluol  and  kept 
in  glass-stoppered  bottles.  Each  daily  period  was  closed  at  the 
same  hour  of  the  morning.  The  fasces  were  transferred  to  the  labora- 
tory as  soon  as  passed.  The  weekly  periods  were  marked  off  in  the 
fagces  by  the  administration  of  charcoal. 

Most  of  the  patients  spent  the  entire  day  in  their  respective 
rooms ;  some  were  permitted  to  go  out  once  a  day  for  a  30  to  45 
minute  walk.  In  each  case  the  patient  had  to  report  to  the  nurse. 

Most  of  the  patients  were  of  an  intelligent  class,  who  understood 
in  a  general  way  the  purpose  of  our  studies  and  were  perfectly  will- 
ing to  cooperate  with  us. 

Special  attention  was  paid  to  the  quantitative  collection  of  urine, 
especially  in  the  female  patients.  They  were  instructed  to  void  the 
urine  before  defalcation,  in  order  to  avoid  any  possibility  of  loss 
while  straining. 

FOOD. 

One  portion  of  the  laboratory  was  converted  into  a  kitchen. 
All  of  the  food  was  prepared  by  the  nurse  and  was  weighed  and  re- 
corded by  one  of  the  investigators  before  it  was  taken  to  the  pa- 
tients' rooms.  The  patients  were  required  to  eat  all  that  was  given 
to  them.  If,  however,  any  food  was  not  eaten  by  the  patient,  it  was 
brought  back  to  the  laboratory  and  weighed  and  subtracted  from 
the  recorded  amount.  (This,  however,  happened  in  a  few  instances 
only.) 

Samples  were  taken  for  analysis  of  all  the  foods  that  were  pre- 
pared. They  were  analyzed  for  their  nitrogen  content  and,  in  many 
cases,  the  sulphur  and  phosphorus  were  also  determined.  Of  the 
foods  prepared  outside  the  laboratory,  as  bread,  large  enough  loaves 
were  obtained  to  last  for  several  days  or  a  week.  An  analysis  was 
made  of  each  individual  loaf.  Butter  was  analyzed  at  the  begin- 
ning of  the  investigation  and  was  found  to  contain  such  a  small 
quantity  of  nitrogen  and  the  individual  samples  varied  to  such  a 
small  extent,  that  it  was  not  deemed  advisable  to  continue  analyzing 
it  and  we  accepted  the  average  figure  obtained,  namely,  0.12%,  as 
the  amount  of  nitrogen  in  butter. 

Foods  eaten  raw,  as  lettuce,  pears,  oranges,  etc.,  were  not 
analyzed  in  our  laboratory.  The  figures  in  "Bulletin  28  of  the  U.  S. 


US       SCHAMBKKG.   KOLMKH,   1UNGKR,  AND  KAI/ISS 

Di-partnu-nt  of  Agriculture,"  17  are  very  accurate  and  we  used  them 
as  the  basis  of  our  calculations. 

MKTHODS  OF  ANALYSES. 

The  totnl  nitrogen  in  the  urine  and  food  was  determined  by 
Kjeldahl. 

Urea  by  Benedict's  latest  method. 

Ammonia  by  Folin's  method. 

Uric  acid  by  Folin's  method. 

Creatinin  by  Folin's  method. 

In  these  analyses  we  were  assisted  by  E.  M.  Frankel  and  H. 
Dubin. 

In  the  charts  are  recorded  the  daily  analyses  of  the  urine,  the 
nitrogen  content  of  the  faeces,  the  nitrogen  in  the  food,  the  daily 
nitrogen  balance  and  the  patient's  weight.*  Under  "diet,"  we  have 
given  in  detail  the  composition  and  character  of  the  food  of  the 
first  day  of  each  period.  The  variation  from  day  to  day  within  a 
given  period  was  very  slight ;  the  main  difference  was  in  the  vege- 
tables. 

For  the  sake  of  convenience,  we  shall  discuss  the  case  of  pa- 
tient Xo.  3  first. 

PATIENT  No.  3.   B.  L. 

FAMILY  HISTORY.  Father  died  at  age  of  42;  cause  of  death  unknown.  Mother 
living,  aged  39  years.  No  psoriasis  in  parents  nor  in  two  sisters  and  three 
brothers. 

PERSONAL  HISTORY.  Patient  #ged  18  years,  was  born  in  Russia.  Had  measles 
and  diphtheria  as  a  child;  she  has  always  been  thin  and  sickly. 

At  the  age  of  13,  the  patient  first  developed  psoriasis.  In  1909,  while  in  Russia, 
she  was  treated  in  a  hospital  for  her  psoriasis,  remaining  in  the  institution  4 
weeks;  in  1911,  she  was  again  under  treatment  in  the  same  hospital  for  8  weeks. 

PRESENT  CONDITION.  The  patient  was  admitted  to  the  Polyclinic  Hospital  on 
Nov.  25,  1912,  with  an  exceedingly  severe  and  widespread  eruption.  She  could 
scarcely  walk  because  of  the  painful  tension  of  the  skin;  the  use  of  the  anus  was 
also  considerably  impaired. 

On  admission,  the  patient  exhibited  a  most  extensive  eruption,  which  was  well 
nigh  universal,  save  for  the  partial  involvement  of  the  face  and  extremities  and 
partial  exemption  of  the  upper  part  of  the  back  and  chest.  The  eruption  upon  the 
trunk  was  of  a  rather  superficial  character;  the  scaling  was  most  profuse,  leading, 
during  the  first  few  days  of  her  hospital  sojourn,  to  the  exfoliation  of  a  quart 
Mason  jarfull  of  lameller  scales  per  day.  The  skin  was  dry,  tense  and  here  and 
there  fissured,  necessitating  the  use  of  vaseline  as  a  lubricant  to  relieve  distress 
and  pain.  Upon  the  arms  and  legs  there  were  large,  intensely  red  plaques,  which 
were  markedly  thickened  and  elevated  above  the  level  of  the  skin.  On  admission, 

*  The  patients  were  weighed  every  day  at  •!•  P.M.  The  clothing  was  weighed 
and  its  weight  subtracted.  In  the  charts,  the  average  weights  for  the  week  are 
given. 


PLATE   XXVIII. — To   Illustrate  Article  on   Research  Studies  in   Psoriasis, 
bv  DBS.   SCHAMBERG,   Koi.MER,   RINGER   and   RAIZISS. 


G<      O 
&* 


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if 


THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


PLATE    XXIX. — To   Illustrate   Article   on   Research   Studies   in   Psoriasis, 
bv  DRS.   SCHAMBERG,   KoLMER,   RIXGER   and   RAIZISS. 


«  — 
rf^ 


bi. 


THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


RESEARCH    STUDIES    IN    PSORIASIS 


the  eruption  on  the  chest  was  limited  by  a  sharp  line  of  demarcation  whose  upper 
border  was  below  the  nipples  anteriorly  and  extended  across  the  shoulder 
blades  posteriorly.  The  chest,  abdomen  and  back  were  the  seats  of  a  confluent 
area  of  psoriasis,  somewhat  suggesting  in  appearance  a  dermatitis  exfoliativa. 
The  scalp  was  diffusely  involved  and  covered  with  scales. 

This  patient  remained  in  the  hospital  for  a  period  of  five  months. 

CLINICAL  CONDITION   IN  .RELATION  TO  THE  DIETARY. 


Admitted  Nov.  25,  1913. 


Nov.   27th 

to 

Dec.  10th 
Dec.  18th 

to 

Jan.  8th 
Jan.  9th 

to 

Jan.  21st 
Jan.  22nd 

to 

March  3rd 


High  Kitrogen  Diet 

18.63  gm. 
per  day. 


Low  Kitrogen  Diet 

6.89  gm. 
per  day. 

High  Nitrogen  Diet 

20.54  gm. 
per  day. 

Low  Nitrogen  Diet 

6  to  7  gm. 
per  day. 


Notes  taken  from  record  charts. 

Dec.  2nd:  "New  papules  have  appeared  on  the 

upper  part  of  the  legs  and  arms." 
Dec.  6th:  "New  papules  upon  the  neck  and  upon 

the   clear   areas   on   the   back." 
Dec.  8th:  "The   eruption   is  spreading   rapidly 

on  the  face." 
Dec.    25th:    "The   skin   is   much   smoother   and 

paler." 
.Jan.  7th:  "The  skin  is  much  paler  in  color  and 

continuing  to  improve.     The  scales  are  finer 

and  less  bulky." 
Jan.  23rd:  "The  feet  are  very  red  and  the  skin 

is  much  more  inflamed  on  the  lower  part  of 

the  body." 


Jan.  28th:  "The   skin  of  the  chest  and   upper 

portions  of  the  arms  and   neck  is  paler." 
Feb.  1st:  "Pronounced  improvement  of  the  skin 

over  buttocks,  thighs  and  legs." 
Feb.  5th:  "Entire  body  much  paler  and  shows 

considerable  improvement." 
Feb.  14th:  "Skin  quite  pale  over  greater  part  of 

body." 
Feb.    18th:   "Skin    is    smooth    and    white    over 

upper  part  of  body  and  neck." 
Feb.  24th:  "There  have  been  no  scales  to  collect 

for  12  days." 
March  3rd:   "Skin   over  greater  part  of  body 

free  of  eruption." 

During  the  period  of  Nov.  27  to  Dec.  3,  1912  (Period  I),  the 
patient  was  placed  on  a  diet  consisting  of  an  average  of  18.63 
grams  of  nitrogen  per  day — 0.45  grams  of  nitrogen  per  kg.  of  body 
weight.  The  total  amount  of  nitrogen  received  with  the  food  for  the 
entire  weekly  period  was  130.4  grams.  During  this  period,  the  pa- 
tient eliminated  in  the  urine  and  faeces  86.29  grams,  which  means 
that  44.11  grams  of  nitrogen  were  retained  in  the  body  during  the 
weekly  period,  or  6.30  grams  per  day. 

During  the  second  week  (Period  2),  the  patient  was  kept  on 
approximately  the  same  diet,  with  the  result  that  136.03  grams  of 
nitrogen  were  ingested.  The  amount  of  nitrogen  eliminated  in  the 


40       SriIAMBKlUJ,  KOLMKH.  KINGKH,  AND  HAI/ISS 

urine  and  f.-eces  during  the  corresponding  period  was  97.39  grams, 
which  means  that  38.(>4  grams  of  nitrogen  were  retained  in  the  body 
—5.52  grams  per  day.  The  patient's  gain  in  weight  above  the 
previous  week  was  0.52  kg. 

It  is  at  once  evident  that  this  patient  presents  a  peculiar  irregu- 
larity in  regard  to  her  nitrogen  metabolism.  A  person  of  her  weight 
on  this  diet  should  have  established  nitrogenous  equilibrium  long  be- 
fore the  end  of  the  two  periods.  It  may  be  argued  that  45  to  49 
calories  per  kg.  of  body  weight,  which  the  patient  received  in  her 
diet,  was  too  high  a  caloric  supply  and  is,  perhaps,  responsible  'for 
the  nitrogen  retention.  But  this  objection  is  not  valid,  because  the 
calories  are  calculated  upon  the  basis  of  food  that  is  ingested;  we 
do  not  take  into  consideration  the  amount  that  passes  through  the 
intestinal  tract  and  comes  out  in. the  faeces,  without  having  ever 
been  resorbed  and  without  having  yielded  any  energy  to  the  body. 
Rubner  18  calculates  the  average  fa?ces  of  a  well-fed  individual  to  con- 
tain 8  to  10%  of  the  gross  caloric  supply  which,  in  establishing  the 
actual  caloric  value  of  a  diet,  has  to  be  subtracted.  However,  to 
eliminate  all  possibility  of  error,  the  patient  was  placed  (in  Period 
3)  on  a  diet  consisting  of  a  gross  caloric  value  of  37.9  calories  per 
kg.  per  day  and  an  amount  of  nitrogen  which  corresponds  to  a  little 
less  than  the  amount  eliminated  in  the  urine  and  faeces  during  the 
first  two  periods.  The  establishment  of  nitrogenous  equilibrium  was 
certainly  expected  during  this  period.  To  our  great  surprise  this 
did  not  occur.  The  nitrogen  in  the  urine,  instead  of  remaining  at 
its  former  level,  dropped  down  to  an  average  of  6.32  grams  per  day. 
The  total  amount  of  nitrogen  received  during  the  course  of  this 
period  was  83.51  grams.  The  amount  of  nitrogen  eliminated  in  the 
urine  and  faeces  was  49.29  grams.  This  means  there  was  a  retention 
of  34.22  grams  of  nitrogen  for  the  week,  or  4.89  grams  per  day. 
The  average  weight  of  the  patient  for  this  period  was  41.80  kg. — a 
gain  of  0.43  kg. 

During  the  first  two  periods,  marked  nitrogen  balances  were 
observed  in  favor  of  the  patient.  The  problem  to  be  solved  was :  Is 
it  a  bona  fide  retention  of  nitrogenous  material  or  is  it  only  an  ap- 
parent retention,  i.e.,  is  the  nitrogen  being  given  off  in  large  quan- 
tities through  a  source  other  than  the  urine  and  faeces?  The  only 
source  of  nitrogen  loss  that  this  patient  presented  was  the  skin. 
The  patient's  skin  had  been  scaling  since  the  beginning  of  the  in- 
vestigation. In  this  period  we  made  a  quantitative  collection  of 
the  scales.  During  the  course  of  the  week,  49  grams  of  scales  were 
collected.  The  scales  contained  11.22%  of  nitrogen,  making  a  total 


RESEARCH    STUDIES    IN    PSORIASIS  41 

of  5.50  grams  of  nitrogen  for  the  week.  As  is  seen,  this  is  a  small 
fraction  of  the  retained  nitrogen  and  fails  completely  to  account 
for  the  positive  nitrogen  balance. 

In  Period  4,  the  patient  was  kept  on  the  same  caloric  supply  as 
in  Period  3,  but  the  nitrogen  intake  was  again  reduced  to  an  amount 
less  than  was  eliminated  in  the  urine  and  faeces  during  the  3rd  pe- 
riod, namely,  an  average  of  6.89  grams  per  day.  As  can  be  seen 
from  the  table  (see  page  52),  the  patient .  failed  to  establish  equi- 
librium even  on  this  diet.  Contrary  to  all  expectations,  the  patient 
retained  1.87,  2.19,  2.16  and  1.69  grams  during  the  first  four  days, 
respectively.  These  retentions  are  the  more  remarkable,  since  nor- 
mally every  change  from  a  high  to  a  low  protein  diet  is  associated 
with  a  negative  nitrogen  balance  (see  page,  35).  The  question 
then  presented  itself:  in  what  form  is  the  nitrogen  retained?  Is  it 
retained  in  the  form  of  the  entire  protein  molecule,  or  in  the  form 
of  end  products,  as  amino-acids  or  urea?  It  also  became  of  great 
importance  to  test  the  kidneys'  eliminative  capacities,  since  it  has 
been  shown  that  in  conditions  of  nephritis,  the  patient's  eliminative 
capacities  for  nitrogenous  end  products  may  be  very  considerably 
interfered  with,19  resulting  in  nitrogenous  retention.  We  therefore 
considered  it  advisable  to  make  a  test,  even  though  our  patient 
showed  no  clinical  evidence  of  kidney  lesion.  On  December  22nd, 
therefore,  20.0  grams  of  urea,  containing  9.33  grams  of  nitrogen, 
were  added  to  the  diet.  Of  this,  8.16  grams  were  recovered  in  the 
urine  of  December  22nd  and  23rd.  The  total  nitrogen  elimination 
in  the  urine  on  December  22nd  rose  to  10.97  grams.  This  experi- 
ment shows  that  the  patient  did  not  suffer  from  any  kidney  dis- 
turbance which  might  account  for  the  nitrogenous  retention  and 
shows,  further,  that  the  patient  does  not  retain  the  nitrogen  in  the 
form  of  urea,  because  .the  extra  urea  that  was  added  to  the  diet 
was  promptly  eliminated.  The  total  amount  of  nitrogen  the  patient 
received  in  her  food  during  this  period  was,  including  the  urea,  57.59 
grams.  She  eliminated  in  the  urine  and  fasces  42.11  grams,  which 
resulted  in  a  positive  nitrogen  balance  of  15.48  grams.  There  were 
58.5  grams  of  scales  during  this  period,  10.20%  of  which  was  nitro- 
gen, equalling  5.97  grams  of  nitrogen.  After  subtracting  this 
from  15.48,  we  still  have  a  net  gain  in  the  body  of  9.51  grams  of 
nitrogen.  The  patient's  average  weight  for  the  period  was  41.35 
kg.,  a  loss  of  0.45  kg.  from  the  previous  week. 

In  Period  5,  the  patient  received  the  same  diet  as  in  Period  4, 
both  quantitatively  and  qualitatively.  No  analyses  were  made  dur- 
ing this  period. 


4^>       SCIIAMBKJUJ,  KOLMKK,   RINGER,  AND  RAIZISS 

In  IVriod  6,  the  same  diet  was  maintained.  On  January  6th 
20.0  grams  of  urea,  containing  9.33  grams  of  nitrogen,  were  again 
added  to  the  diet.  Of  this,  9.16  grams  were  recovered  in  the  urine. 
Almost  quantitative  elimination.  The  total  amount  of  nitrogen 
ingested  during  this  period  was  43.62  grams;  42.5  grams  of  scales 
were  collected,  containing  10.66%,  or  4.53  grams  of  nitrogen. 
Again,  we  have  a  net  nitrogen  retention — in  this  case  of  17.04 
grams.  In  spite  of  this  retention  of  nitrogenous  material,  there  was 
a  considerable  loss  of  body  weight.  The  average  body  weight  for 
this  period  was  40.1  kg.,  a  loss  of  1.25  kg.  in  two  weeks.  This  indi- 
cates clearly  that  38  to  42  calories  per  kg.  of  body  weight  was  not 
sufficient  to  cover  the  patient's  bodily  needs.  This  fact  makes  nitro- 
genous retention  the  more  remarkable.  During  these  periods  of  low 
nitrogen  diet  the  skin  became  much  paler,  smooth,  and  continued  im- 
proving. The  scales  became  finer  and  less  bulky. 

In  Period  7,  the  patient  was  placed  on  a  diet  consisting  of  20.54 
grams  of  nitrogen  per  day,  with  an  energy  supply  in  the  food  of 
53.6  calories  per  kg.  of  body  weight.  The  nitrogen  retention  in  the 
body  during  the  two  weeks  was  enormous,  amounting  to  66.10  grams 
in  Period  7  and  to  60.94  grams  in  Period  8.  A  total  retention  of 
127.04  grams  of  nitrogen  in  two  weeks.  If  we  subtract  from  this 
the  1.54  grams  of  nitrogen  found  in  the  scales  of  Period  7  and  the 
5.58  grams  of  nitrogen  found  in  the  scales  and  perspiration  of 
Period  8,  there  remains  a  positive  nitrogen  balance  of  119.88  grams 
in  a  period  of  13  days.  A  point  of  great  significance  in  this  con- 
nection is  the  fact  that  in  spite  of  the  retention  of  66  grams  of 
nitrogen — 412.5  grams  of  protein — in  Period  7,  the  patient's  aver- 
age weight  for  the  period  remained  absolutely  constant.  During 
the  8th  period,  however,  there  was  a  gain  of  0.75  kg.  We  call  spe- 
cial attention  to  this,  because  we  shall  later  discuss  the  subject  in 
detail. 

When  we  analyze  the  daily  relationship  that  exists  between  the 
ingested  nitrogen — either  in  the  form  of  urea  or  protein — and  the 
daily  nitrogenous  elimination  in  the  urine,  we  get  an  insight  into 
the  mechanism  of  the  nitrogenous  retention.  This  is  brought  out  in 
table  No.  1. 

This  table  shows  that,  after  the  addition  of  urea  to  the  diet,  the 
nitrogen  rise  in  the  urine  was  very  prompt — rising  to  almost  11 
grams  in  one  day.  The  addition  of  a  much  larger  amount  of  nitro- 
gen in  the  form  of  protein,  milk  and  meat,  resulted  in  a  compara- 
tively slight  rise  in  the  urinary  nitrogen,  the  amount  increasing 
slowly  but  steadily,  for  only  on  the  sixth  day  did  it  exceed  10  grams. 


RESEARCH    STUDIES    IN    PSORIASIS 


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44        SCIIAMBKIU;,  KOLMKH,  UINGKll,  AM.   KAI/ISS 

This  ami  also  tlu1  following  days  show  Kith  what  remarkable  tenacity 
the  patient's  body  holds  on  to  the  nitrogen  of  tlie  protein. 

In  considering  all  the  sources  of  nitrogen  excretion  in  a  human 
individual,  one  must  bear  in  mind  that  some  nitrogenous  material 
is  excreted  through  the  skin  with  the  perspiration.  On  January 
17th  the  perspiration  of  the  patient  was  collected  as  follows:  she 
wore  a  suit  of  woolen  underwear  which  had  previously  been  washed 
in  alcohol  and  dilute  hydrochloric  acid.  This  suit  was  worn  for 
three  days,  .January  17th,  18th  and  19th.  The  suit  was  then  washed 
in  alcohol  and  dilute  hydrochloric  acid  solution.  The  collected 
washings  were  evaporated  and  the  nitrogen  determined  by  Kjeldahl. 
For  the  three  days  there  were  found  1.02  grams  of  nitrogen  (0.34 
gram  per  day).  During  the  two  days  following,  January  20th  and 
21st,  0.59  gram  of  nitrogen  was  collected  in  the  perspiration  (0.30 
gram  per  day).  These  amounts  are  within  the  range  of  the  normal 
and  do  not  show  any  excessive  nitrogen  excretion  through  the  skin. 

During  these  two  periods  of  high  nitrogen  diet  and  high  nkrogen 
retention,  the  patient's  skin  became  much  more  inflamed  on  the  lower 
part  of  the  body. 

From  the  results  thus  far  obtained  we  noticed  a  marked  beneficial 
effect  that  the  low  protein  diet  produced  on  the  course  of  the  psoria- 
sis, and  that  the  high  protein  diet  tended  very  strongly  to  stimulate 
the  spread  of  disease;  we  therefore  decided  to  keep  the  patient 
on  a  low  protein  and  largely  vegetable  diet.  In  Period  9  the  patient 
received  a  diet  consisting  of  44.3  calories  per  kg.  of  body  weight, 
and  6.58  grams  of  nitrogen  per  day  (0.164  gram  of  nitrogen  per 
kg.).  The  total  amount  of  nitrogen  received  in  the  food  for  the 
period  was  46.08  grams.  The  amount  eliminated  in  the  urine  and 
fasces  was  35.76  grams.  During  the  three  days,  January  23rd  to 
25th  inclusive,  1.71  grams  of  nitrogen  were  collected  in  the  scales 
and  0.86  gram  in  the  perspiration,  a  total  of  2.47  grams.  When 
calculated  for  the  week,  we  have  6.0  grams  of  nitrogen  eliminated 
through  the  scales  and  perspiration.  This  leaves  a  net  retention  of 
4.32  grams.  The  average  weight  was  40.15  kg. — a  loss  of  0.75  kg. 

In  Period  10,  the  diet  was  the  same  as  in  the  preceding  period 
with  regard  to  its  nitrogen  content,  but  it  contained  a  lower  caloric 
value — 34.9  calories  per  kg.,  or  1381  calories  per  day.  When  we 
subtract  from  this  value  the  caloric  value  of  the  unresorbed  food 
in  the  faeces,  which  must  have  been  high  considering  the  high  amount 
of  nitrogen  in  the  faeces,  and  estimate  the  net  caloric  supply  on  the 
basis  of  the  patient's  body  surface  area,  we  find  that  this  was  a  very 
poor  diet  as  far  as  the  energy  supply  was  concerned.  The  patient's 


45 

average  weight  was  39.60  kg. — a  loss  of  0.55  kg. — which  means 
that  the  patient  burned  some  of  her  own  body  fat.  In  spite  of  it  all, 
however,  there  was  a  marked  and  persistent  nitrogen,  retention, 
which  amounted  to  14.47  grams  for  the  week,  or  2.07  grams  per 
day.  Associated  with  this,  there  was  plainly  noticeable  a  marked 
and  gradual  improvement  in  the  condition  of  the  patient's  skin. 
The  amount  of  scales  for  the  week  was  only  3.5  grams,  with  a  nitro- 
gen content  of  0.386  grams. 

In  Periods  11  and  12,  the  same  diet  was  continued  with  less  than 
7  grams  of  nitrogen  in  the  food  per  day.  The  caloric  value  was 
raised,  by  the  addition  of  125  grams  of  cream  and  100  grams  of 
cornstarch,  to  about  1,800  calories  per  day  (46.4  per  kg.).  (See 
details  in  chart,  p.  58.)  The  patient's  weight  during  Period  11  fell 
to  .39. 15  kg.,  a  loss  of  0.45  kg.,  but  it  returned  to  39.60  kg.  in  Per- 
iod 12.  During  the  two  periods,  the  nitrogen  balance  persisted  on 
the  positive  side,  to  the  extent  of  over  two  grams  per  day,  which 
amounted  to  16.75  grams  for  Period  11  and  17.46  grams  for  Period 
12.  There  was  no  measurable  scaling  during  these  two  periods  and 
the  perspiration  collected  during  Period  12  contained  only  0.708 
grams  of  nitrogen. 

These  nitrogen  retentions,  extending  over  so  long  a  period,  are 
the  very  highest  that  have  ever  been  recorded  in  human  individuals 
kept  on  such  a  low  protein  intake. 

In  Period  13,  53.3  grams  of  nitrogen  were  ingested  and  38.99 
grams  were  eliminated  in  the  urine  and  faeces,  resulting  in  a  reten- 
tion of  14.31  grams  of  nitrogen.  The  average  body  weight  remained 
constant. 

In  Period  14,  40.84  grams  of  nitrogen  were  ingested  and  34.69 
grams  were  eliminated — a  retention  of  6.15  grams.  The  body  weight 
was  not  recorded  during  this  week. 

During  the  last  two  periods  (13  and  14),  a  normal  individual, 
Miss  W.,  an  employee  of  the  hospital,  was  placed  on  exactly  the 
same  diet  as  was  Patient  No.  3.  One  of  the  objects  of  that  experi- 
ment was  to  demonstrate  the  difference  between  the  behavior  of  nor- 
mal and  psoriatic  individuals  with  regard  to  the  maintenance  of 
nitrogenous  equilibrium  when  on  a  diet  of  about  7  grams  of  nitrogen 
per  day. 

The  difference  is  very  striking.  Whereas  Miss  W.  showed  a 
negative  nitrogen  balance  during  these  two  periods,  i.e.,  catabolized 
more  than  she  ingested,  Patient  No.  3  showed  a  retention  of  over 
20  grams. 

This  experiment  presents  several  points  of  interest  which  will 


40       SCHAMHKKC;,  KOLMKR,  RINGER,  AND  RAIZISS 

be  taken  up  in  u  subsequent  paper.  The  most  significant  tiling  here 
w  the  fact  that  a  psoriatic  indiiidual  can  retain  nitrogen  on  a  diet 
on  which  a  normal  individual  fails  to  even  maintain  equilibrium. 

It  is  seen  from  the  above  that,  without  any  local  treatment,  a 
severe  case  of  psoriasis  became  almost  entirely  cleared  during  a  pe- 
riod in  which  the  diet  was  especially  low  in  its  nitrogen  content.  It 
was  also  observed  that  during  the  periods  in  which  the  nitrogen  con- 
tent in  the  food  was  high,  the  disease  spread  considerably.  These 
results  led  us  to  suspect  that  there  was  some  intimate  relationship 
between  the  protein  content  of  the  food  and  the  severity  of  the  dis- 
ease. At  this  stage  of  the  investigation,  the  patient's  skin  "was  free 
of  eruption  over  the  greater  part  of  the  body,"  and  the  scales  were 
reduced  to  immeasurable  quantities.  We  therefore  decided  to  place 
the  patient  on  a  high  protein  diet  with  the  object  of  testing  the  cor- 
rectness of  our  supposition. 

In  Periods  15,  16,  17  and  18,  the  patient  was  kept  on  a  diet  simi- 
lar to  that  of  Periods  7  and  8.  The  average  nitrogen  intake  per 
day  was  between  21  and  22  grams.  The  amount  of  nitrogen  ingested 
in  Period  15  was  150.77  grams.  The  amount  excreted  in  the  urine 
and  fa?ccs  was  105.99  grams ;  a  retention  of  44.78  grams  per  week  or 
6.40  grams  per  day. 

The  reader  will  please  note  the  amount  of  urinary  nitrogen  in 
Periods  7  and  8  and  compare  them  with  those  of  Periods  15,  16  and 
17.  The  highest  amount  eliminated  then  was  11.15  grams  (on  Jan- 
uary 21st)  ;  the  nitrogen  elimination  in  the  latter  periods  exceeded  17 
grams  per  day.  In  Periods  7  and  8,  when  the  disease  was  very 
active,  the  patient,  on  a  diet  of  20.54  and  21.07  grams  of  nitrogen 
per  day,  retained  11.02  and  8.79  grams  of  nitrogen  for  the  two 
periods,  respectively. 

In  Periods  15,  16  and  17,  when  the  activity  of  the  disease  was 
considerably  checked  and  the  patient's  skin  was  rapidly  improving, 
the  administration  of  a  diet  similar  to  the  above  was  accompanied 
by  a  retention  of  6.40  grams  per  day  in  Period  15,  4.40  grams  in 
Period  16  and  only  2.36  grams  in  Period  17. 

In  Period  16, 153.52  grams  of  nitrogen  were  ingested  and  122.68 
grams  excreted  in  the  urine  and  faeces,  resulting  in  a  retention  of 
30.84  grams  or  4.40  grams  per  day.  The  patient's  average  weight 
in  this  period  was  41.6  kg. 

In  Period  17,  150.79  grams  were  ingested  and  134.24  grams  ex- 
creted, resulting  in  a  retention  of  16.55  grams.  The  patient's  aver- 
age weight  was  42.0  kg.,  a  gain  of  0.4  kg. 

In  Period  18,  163.99  grams  of  nitrogen  were  ingested  and  134.98 


RESEARCH    STUDIES    IN  .PSORIASIS  47 

were  eliminated  in  the  urine  and  faeces,  resulting  in  a  retention  of 
29.01  grams.  The  patient's  average  weight  was  42.5  kg.,  a  gain 
of  0.5  kg.  On  April  1st,  20  grams  of  urea,  containing  9.33  grams 
of  nitrogen,  were  added  to  the  diet.  The  nitrogen  elimination  in 
the  urine  rose  from  16.20  to  25.05  grams.  Of  the  urea  nitrogen, 
8.28  grams  were  recovered  in  the  urine.  This  shows  that,  even  on 
a  high  protein  diet,  the  kidneys'  eliminative  capacity  for  the  princi- 
pal end  product  of  protein  catabolism  is  not  in  any  way  disturbed. 

Period  19  consisted  of  10  days  and  was  divided  into  two  halves. 
During  the  first  half,  a  very  high  protein  diet  was  given,  amounting 
to  28.08,  28.67,  27.22,  29.61  and  28.61  grams  of  nitrogen  per  day. 
During  this  period  there  were  obtained  the  highest  figures  for  elimi- 
nated nitrogen,  the  highest  point  being  reached  on  the  10th  of  April, 
when  23.85  grams  of  nitrogen  were  eliminated.  The  amount  of  nitro- 
gen retained  during  these  5  days  was  26.17  grams.  On  April  12th 
the  nitrogen  in  the  food  was  reduced  to  5.64  grams.  This  low  nitro- 
gen diet  was  continued  for  the  following  4  days,  namely,  5.75,  5.73, 
6.15  and  5.39  grams  of  nitrogen  per  day.  Contrary  to  our  previous 
experiences,  no  equilibrium  was  established  and  the  patient  remained 
in  negative  nitrogen  balance. 

On  April  16th  the  patient  left  the  hospital. 

SUMMARY  OF  RESULTS  OBTAINED  IN  THE  STUDY  OF  PATIENT  No.  3. 

When  we  come  to  summarize  the  results  obtained  from  a  study 
of  this  case,  two  important  facts  stand  out  prominently: 

I.  The  very  marked  and  persistent  nitrogen  retention  through- 
out the  entire  course  of  the  investigation. 

II.  The  relationship  that  appears  to  exist  between  the  amount 
of  nitrogen  in  the  food  and  the  course  of  the  disease  (see  table  No.  2) . 

Throughout  the  investigation  of  this  case,  which  lasted  128  days, 
the  patient  ingested  in  her  food  1,816.29  grams  of  nitrogen.  During 
this  period,  she  eliminated  in  the  urine  and  faeces,  1,323.97  grams  of 
nitrogen,  which  leaves  a  positive  balance  in  favor  of  the  body  of 
492.32  grams.  To  get  the  actual  amount  of.  nitrogen  retained  in 
the  body,  we  must  subtract  the  amount  of  nitrogen  given  off  in  the 
form  of  scales  and  perspiration.  The  scales  were  collected  in  most 
of  the  periods  in  which  exfoliation  took  place.  Their  analyses 
follow : 


48       SCHAMBKUG,  KOLMKK,  KINGKK,  AND  RAIZISS 

Period   1.  Not   analj  ml.     6.0    grams   of    nitrogen    assumed. 

2.  Not  analyzed.     6.0  grains  of  nitrogen  assumed. 

8.  5..50  grams  of  nitrogen. 

1.  ,>.97  grams  of  nitrogen. 

5.  Not  analyzed.     6.0  gnnrs  of  nitrogen  assumed. 

6.  4.53  grains  of  nitrogen. 

7.  1.54  grams  of  nitrogen. 

8.  3.5)7  grams  of  nitrogen. 

9.  1.71   grams  of  nitrogen. 

10.  0.39  grams  of  nitrogen. 

After  the  10th  period,  there  was  so  little  scaling  that  its  collec- 
tion became  impossible.  The  total  amount  of  nitrogen  collected 
through  the  scaling  was  23.6  grams.  If  we  assume  the  maximum 
amount  of  nitrogen  to  have  been  lost  in  the  scales  of  the  periods  in 
which  no  analyses  were  made,  then  the  total  amount  of  nitrogen  thus 
lost  would  not  exceed  51.6  grams. 

The  perspiration  was  collected  during  the  period  of  January  17th 
to  19th  and  found  to  contain  1.02  grams  of  nitrogen — 0.34  grams 
per  day.  During  January  20th  and  21st,  0.59  grams  were  found 
— 0.30  grain  per  day.  During  January  23rd  to  25th,  0.86  gram 
were  collected — 0.29  gram  per  day.  Between  February  12th  to 
18th,  0.71  gram  of  nitrogen  was  collected  in  the  perspiration — 0.10 
gram  per  day.  We  are  inclined  to  attribute  the  high  figures  in  the 
first  examinations  to  the  inclusion  of  small  particles  of  exfoliated 
epithelium  in  the  underwear,  which  were  analyzed  with  the  perspira- 
tion (the  patient  scaled  quite  freely  during  that  period)  and  are  of 
the  opinion  that  0.1  gram  per  day  is  the  more  correct  value  for  nitro- 
gen loss  through  perspiration,20  We  shall,  however,  accept  0.3 
gram  per  day  as  the  basis  of  calculation  of  the  approximate  amount 
of  nitrogen  lost  through  perspiration.  In  128  days  the  patient 
could  not  have  lost  more  than  38  grams  of  nitrogen  in  this  way. 
When  we  add  this  to  the  51.6  grams  lost  in  the  scales,  we  find  a  total 
loss  of  89.6  grams  through  the  skin.  This  leaves  a  net  nitrogen  bal- 
ance of  492.3  —  89.6  =  402.7  grams.  This  amount  of  nitrogen 
must  have  been  added  to  the  patient's  body  during  the  course  of  this 
investigation. 

From  the  above  data,  it  seems  that  this  patient,  who  was  suf- 
fering from  a  most  widespread  psoriasis,  had  a  pronounced  exten- 
sion of  the  eruption  under  a  relatively  high  nitrogen  dietary  during 
the  first  two  weeks  of  her  hospital  sojourn  (Fig.  1).  After  the  in- 
auguration of  a  low  nitrogen  diet,  the  inflammation  in  the  skin  and 
the  amount  of  scaling  gradually  became  less.  Later,  a  two  weeks' 
regime  of  high  nitrogen  appeared  to  cause  increased  inflammation, 
the  latter  subsiding  after  the  institution  of  a  low  nitrogen  diet. 


RESEARCH    STUDIES    IN    PSORIASIS 


49 


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PATIENT  NO.  3.  MISS  B.  L.  PERIOD  XI 

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RESEARCH    STUDIES    IN    PSORIASIS  69 

From  then  on,  under  a  prolonged  low  nitrogen  dietary,  the  patient 
continuously  improved,  until,  on  discharge  from  the  hospital,  but  a 
bare  vestige  of  the  eruption  remained  in  a  few  isolated  areas  (Fig. 
2).  Curiously,  a  band-like  streak  of  eruption  (Fig.  4)  on  the  left 
buttock  and  thigh,  persisted  for  several  months  after  the  eruption 
had  practically  disappeared  elsewhere.  Under  the  continuance  of 
the  diet  prescribed  after  the  discharge  of  the  patient,  this  band 
practically  faded  away. 

While  the  trunk  in  Fig.  1  exhibits  a  very  superficial  type  of  the 
disease,  there  were  large,  thickened  and  intensely  hyperaemic  patches 
on  the  extremities. 

During  the  last  few  weeks  of  the  patient's  hospital  sojourn,  she 
was  placed  upon  an  increased  nitrogen  diet,  without  any  material 
aggravation  of  the  eruption ;  at  this  time,  however,  although  she  still 
retained  nitrogen,  the  amount  of  retention  was  less  than  during  any 
previous  period  of  high  nitrogen  diet. 

These  patches  all  disappeared  without  the  use  of  any  active 
medicament.  Vaseline  was  used  on  the  eruption  to  alleviate  the  ex- 
cessive dryness  and  tension,  which  gave  rise  to  the  keenest  distress 
to  the  patient.  No  other  local  treatment  and  no  internal  treatment 
was  employed  whatsoever. 

PATIENT  No.  4. 

N.  N.;  male,  age,  33;  born  in  Russia. 

He  does  not  recall  the  diseases  of  early  life.  He  served  four  years  in  the 
Russian  Army,  during  which  time  he  suffered  an  attack  of  jaundice  lasting  five 
weeks.  He  never  had  rheumatism.  No  history  of  psoriasis  in  parents  or  any 
other  member  of  the  family. 

PRESENT  CONDITION.  The  patient  is  short  and  thick  set;  height,  5  feet  6  inches; 
weight  143  pounds.  The  first  attack  of  psoriasis  was  experienced  seven  years  ago; 
he  has  suffered  pretty  constantly  with  more  or  less  eruption  since  then. 

The  patient  was  admitted  to  the  Polyclinic  Hospital  on  Dec.  26,  1912.  On 
admission,  he  exhibited  extensive  figurate  psoriasis  covering  a  considerable  portion 
of  the  cutaneous  surface.  (Figs.  5  and  7).  The  scalp  was  markedly  involved 
and  a  broad  band  of  eruption  extended  to  a  depth  of  one  inch  around  the  frontal 
border  of  the  hair.  The  eyebrows  and  mustache  were  also  the  seat  of  eruption. 
The  chest  and  abdomen  exhibited  huge,  diffuse  patches  covering  about  two  thirds 
of  the  surface.  The  back,  from  the  nape  of  the  neck  to  the  sacrum,  was  almost 
completely  covered  by  a  huge,  single,  unbroken  patch.  The  only  free  areas  were 
the  right  scapular  region,  the  left  shoulder  and  the  lateral  aspects  of  the  lumbar 
region.  The  patient  complained  of  tenseness  and  impaired  suppleness  of  the  skin, 
which  caused  pain  and  bleeding.  The  patches  were  of  a  deep-red  color,  palpably 
elevated  and  covered  with  a  moderately  thick  layer  of  scales. 

The  arms  and  legs  were  beset  with  a  number  of  psoriasis  plaques,  varying 
in  diameter  from  a  pea  to  the  palm  of  the  hand.  The  nails,  both  of  the  hands 
and  feet,  were  severely  affected,  showing  marked  subungual  thickening  and  pro- 
nounced pittings.  Under  a  low  protein  diet  the  patches  graduallv  lost  their 
infiltration  and  subsided  to  the  level  of  the  skin. 


70       SCHAMHKlUi,   KOLMKK,  KINGKK,  AND  KAIZISS 

The  patient  was  under  the  necessity  of  supporting  his  family  and  was  able 
to  remain  only  a  limited  period  of  time  in  the  hospital  (seven  weeks).  He  was 
discharged  on  Fell.  13,  1913. 

I'ndcr  the  use  of  a  chrysnrohin  ointment,  20  grains  to  the  ounce  of  vaseline, 
applied  two  weeks  liefore  his  discharge,  the  eruption  rapidly  improved  and,  with- 
out any  interruption,  progressed  to  the  point  of  disappearance. 

Examined  on  March  30,  1913,  the  entire  surface  of  the  face,  scalp,  trunk, 
arms  and  legs  wa.s  free  of  the  eruption,  save  for  a  few  ill-defined  and  super- 
ficial, scaly  areas  on  the  sacrum  and  legs.  The  nails  exhibit  a  marvelous  im- 
provement, having  lost  their  thickening  and  showing,  in  their  new  proximal  por- 
tion, healthy  nail  tissue. 

No  treatment  was  applied  to  the  scalp;  no  internal  treatment  whatsoever  was 
employed.  The  patient  after  discharge  from  the  hospital  faithfully  continued  the 
diet  prescrilwd  for  him. 

On  January  1,  1913,  the  patient  was  placed  on  a  diet  consisting 
of  a  little  more  than  7  grams  of  nitrogen  per  day.  The  total  amount 
of  nitrogen  ingested  during  Period  1  (8  days)  was  67.72  grams. 
The  amount  of  nitrogen  eliminated  in  the  urine  and  fjeces  was  62.4)1 
grams,  resulting  in  a  positive  balance  of  5.31  grams.  During  the 
period,  9.5  grams  of  scales  were  exfoliated  from  the  skin,  11.19% 
of  which  was  nitrogen,  equalling  1.06  grams  which  has  to  be  sub- 
tracted, leaving  a  net  gain  to  the  bod}r  of  4.25  grams.  The  patient's 
average  weight  for  the  period  was  64.9  kg.  The  caloric  value  of  the 
food  was  about  1800  calories,  or  about  28  calories  per  kg.  of  body 
weight. 

On  January  6th,  20  grams  of  urea,  containing  9.33  grams  of 
nitrogen,  were  added  to  the  diet.  Of  this,  8.2  grams  were  recovered 
during  the  days  of  January  6th  and  7th. 

In  Period  2,  the  patient  was  placed  on  a  diet  consisting  on  an 
average  of  27.06  grams  of  nitrogen  per  day,  with  a  caloric  value 
of  2670  per  day,  or  4-1.2  per  kg.  The  total  amount  of  nitrogen 
ingested  in  the  period  was  162.37  grams.  The  amount  eliminated 
in  the  urine  and  fa>ces  was  105.48  grams ;  3.5  grams  cf  scales 
were  collected,  containing  0.39  gram  of  nitrogen,  which  leaves  a  net 
retention  of  56.50  grams  of  nitrogen.  The  average  weight  of  the 
patient  for  the  period  was  64.8  kg. — a  loss  of  0.1  gram. 

Here,  we  have  a  tremendous  retention  of  nitrogen,  corresponding 
to  853  grams  of  pure  protein,  while  the  pateint  is  on  a  rich  caloric 
supply,  without  any  gain  in  body  weight.  This  is  very  remarkable, 
for  the  same  observation  was  made  in  Patient  3,  Period  7. 

In  Period  3,  the  patient  was  kept  on  approximately  the  same 
diet,  receiving  194.77  grams  of  nitrogen  (an  average  of  27.82  grams 
per  day)  and  about  2800  calories  per  day.  The  amount  of  nitrogen 
eliminated  in  the  urine  and  faeces  was  147.62  grams.  In  3  grams  of 
scales  there  were  found  0.34  gram  of  nitrogen.  This  leaves  a  posi- 


PLATE    XXX. — To   Illustrate   Article   on    Research   Studies   in   Psoriasis, 

bv    DRS.     SCHAMBERG,     Koi.SIEU.     RlKGER     and     RAIZISS. 


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THE  JOUKHAL  or  CUTANEOUS  DISEASES,  November,  1913. 


PLATE   XXXI. — To   Illustrate   Article  on   Research   Studies  in   Psoriasis, 
bv   Bits.   SCIIAMBERG,   Koi.MER,   RINGER   and   RAIZISS. 


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RESEARCH    STUDIES    IN    PSORIASIS 


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74        SCHAMHKIKi,   KOLMKK,   HINCiKU,  AND  RAIZISS 


PATIENT  NO.  4.  MR.  N.  PERIOD  IV 

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RESEARCH    STUDIES    IX    PSORIASIS 


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RESEARCH    STUDIES    IN    PSORIASIS  77 

live  nitrogen  balance  of  46.81  grams.  The  patient's  average  weight 
was  65.8  kg. — a  gain  of  1.0  kg. 

In  Period  4,  the  nitrogen  in  the  diet  was  reduced  to  an  average 
of  7.04  grams  per  day.  In  this  case  the  change  in  diet  from  high 
to  low  protein  caused  a  negative  nitrogen  balance  which  persisted  for 
about  3  days.  Beginning  with  the  fourth  day,  the  nitrogen  balance 
became  positive  and  remained  so  until  the  end  of  the  investigation. 
The  total  amount  of  nitrogen  ingested  during  the  course  of  the  week 
was  49.27  grams.  The  amount  eliminated  in  the  urine  and  fasces 
was  51.51  grams  and  0.25  gram  was  found  in  the  2.2  grams  of  scales 
which  were  collected  during  the  period.  This  leaves  a  net  loss  to  the 
body  of  2.49  grams.  The  average  body  weight  was  65.4  kg. — a  loss 
of  0.4  kg. 

In  Period  5,  the  diet  given  contained  the  same  amount  of  nitrogen 
as  did  the  diet  in  the  preceding  perio.d,  but  with  a  lower  caloric 
supply,  namely,  1471  calories  per  day,  or  22.7  per  kg.  The  amount 
of  nitrogen  ingested  was  49.66  grams.  In  the  urine  and  faeces,  39.17 
grams  were  eliminated  and  0.17  gram  in  the  scales.  This  leaves  a 
retention  of  10.32  grams.  The  patient's  average  weight  was  65.0 
kg.,  a  loss  of  0.4  kg. 

In  Period  6,  the  diet  was  the  same  as  regards  its  nitrogen  content, 
but  it  was  of  a  higher  caloric  value,  2017  calories  per  day,  or  31.2 
per  kg.  The  total  amount  of  nitrogen  ingested  was  52.63  grams. 
The  amount  eliminated  in  the  urine  and  faeces  was  40.91  grams,  re- 
sulting in  a  positive  nitrogen  balance  of  11.72  grams.  The  pa- 
tient's average  weight  was  64.7  kg.,  a  loss  of  0.3  kg. 

On  February  llth  the  patient  left  the  hospital. 

SUMMARY  OF  THE  RESULTS  OBTAINED  IN  THE  STUDY  OF 
PATIENT  No.  4. 

The  patient  presented  a  case  of  psoriasis  of  more  than  ordinary 
severity.  The  results  obtained  in  this  case  are  jn  absolute  agree- 
ment with  those  obtained  with  Patient  No.  3.  The  patient  pre- 
sented some  remarkable  peculiarities  in  his  protein  metabolism ;  first, 
in  being  able  to  store  nitrogen  easily,  even  when  receiving  only  7 
grams  per  day,  with  a  caloric  supply  of  only  22.7  grams  per  kg. ; 
secondly,  in  being  able  to  store  tremendous  quantities  of  nitrogen 
when  on  a  high  protein  diet ;  and  thirdly,  in  showing  improvement  in 
the  condition  of  his  skin  when  on  a  low  protein  diet  (see  table  No.  3). 

During  his  stay  of  42  days  in  the  hospital,  the  patient  ingested 
576.42  grams  of  nitrogen.  He  eliminated,  in  the  urine  and  faeces, 


78     SCHAMBKIH;,  KOLMKR,  RINGER,  AND  RAI/ISS 


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RESEARCH    STUDIES    IN    PSORIASIS  79 

44<7.10  grams.  This  leaves  a  positive  balance  of  129.32  grams. 
Severe  as  the  case  was,  the  amount  of  scaling  was  comparatively 
slight. 

The  following  amounts  of  nitrogen  were  found  in  the  collect 
scales  for  each  of  the  periods : 

Period  1 1.06  grains. 

2 0.39  " 

3 0.34 

4 0.25 

5 0.17  " 

6 0.00  " 

The  total  amount  of  nitrogen  eliminated  in  the  scales  for  the 
entire  period  of  investigation  was  2.21  grams.  When  we  add  to 
this  the  amount  of  nitrogen  lost  in  the  perspiration  (assuming  0.3 
gram  per  day,  which  equals  12.6  grams  for  the  entire  period)  the 
total  amount  of  nitrogen  eliminated  through  the  skin  could  not  have 
exceeded  14.8  grams.  As  the  positive  balance  over  the  urinary  and 
faecal  nitrogen  amounted  to  129.32  grams,  on  subtracting  14.8 
grams,  we  find  a  net  retention  of  114.5  grams  of  nitrogen,  an  amount 
which  is  present  in  716  grams  of  protein. 

PATIENT  No.  5. 
H.   B.;  male;   age,  47;  born   in  the   United   States. 

FAMILY  HISTORY.  His  father  died  at  the  age  of  75.  For  ten  years  he  had  a 
large  ulcer  in  the  groin.  For  four  or  five  years  prior  to  his  death,  he  had  a 
"generalized  scaly  eczema,"  so  diagnosed  by  a  well-known  dermatologist.  His 
mother  is  living  and  well  at  the  age  of  77.  No  other  members  of  the  family  ever 
had  any  skin  trouble. 

PREVIOUS  HISTORY.  The  patient  has  been  married  22  years.  His  wife  is  living 
and  well.  The  first  pregnancy  resulted  in  miscarriage.  There  are  three  children, 
all  well  and  robust;  the  eldest  is  19  years  old.  The  patient  had  measles  and 
scarlet  fever  in  childhood.  He  had  gastritis  at  the  age  of  19  and  jaundice  on 
several  occasions.  He  is  subject  to  "bilious  attacks."  He  has  been  constipated 
for  the  past  ten  or  twelve  years.  At  the  age  of  20,  he  had  a  "chancroid,"  which 
lasted  about  four  weeks  and  was  treated  with  local  applications  only;  he  never 
had  any  manifestations  suspicious  of  lues.  In  1908,  a  boil-like  lesion  began  below 
the  left  knee,  which  grew  to  a  plaque  about  2  inches  in  diameter  and  became 
elevated  above  the  skin  about  14  to  i£  inch,  with  a  papillomatous  surface;  a 
diagnosis  of  sarcoma  was  made.  In  1910,  an  operation  was  performed  to  re- 
move the  growth,  but  it  was  found  to  extend  too  deep.  A  month  later,  the  leg 
was  amputated  above  the  middle  of  the  thigh.  Enlarged  glands  developed  seven 
months  later  (May  1911)  in  the  left  groin,  and  were  excised;  the  wound  failing 
to  heal,  a  second  operation  was  performed  on  the  glands  in  July,  1911,  with 
successful  result.  No  microscopic  examination  of  the  growth  appears  to  have 
been  made. 

PRESENT  DISEASE.  The  patient  first  developed  psoriasis  17  years  ago,  and  has 
never  been  free  from  the  eruption  since  then.  He  has  usually  had  large  areas 


SO       SCH  AMI*  ERG,  KOLMEK,  RINGER,  AND  RAIZISS 

of   the   body   covered.      The   eruption   is   worse   in   winter   and   usually   better   in 
summer. 

The  patient  WHS  admitted  to  the  hospital  on  Jan.  16,  1913.  On  admission,  he 
exhibited  a  most  extensive  eruption,  covering  the  face,  scalp,  trunk  and  extremities. 
The  face  was  in  large  part  covered  with  superficial,  reddish  patches,  particularly 
in  the  bearded  region.  The  trunk,  which  is  shown  in  Figs.  9  and  11,  was  the  seat 
of  extensive,  irregular  patches,  which  were  considerably  infiltrated  and  covered 
with  heavy  scales.  The  legs  and  arms  were  enveloped  in  extensive,  thickened 
patches,  which  involved  about  two  thirds  of  the  area  of  the  extremities. 

The  patient  was  on  a  high  nitrogen  diet  for  five  days  from  the 
date  of  admission ;  during  this  period,  the  eruption  on  the  face  be- 
came distinctly  worse:  this  was  independently  commented  upon  by 
the  physician  in  attendance,  by  the  nurse  and  by  the  patient's  sister. 

Later,  the  patient  was  placed  upon  a  low  nitrogen  diet  and  kept 
upon  this  diet  for  the  greater  period  of  his  hospital  sojourn.  The 
patient  was  discharged  from  the  hospital  on  February  28,  1913. 
At  this  time  a  vast  improvement  was  evident  in  the  eruption.  Large 
areas  of  the  body  had  become  pale  and  were  relatively  free  of  erup- 
tion. To  properly  appreciate  the  extent  of  improvement,  attention 
is  directed  to  Figs.  9,  10,  11,  and  12.  The  interval  elapsing  be- 
tween the  taking  of  the  photographs  was  about  70  days. 

The  scalp,  which  was  very  scaly  on  admission,  cleared  up  without 
any  remedial  application  whatsoever.  The  patient  received  no  inter- 
nal treatment  and  nothing  was  used  locally  except,  occasionally,  a 
little  vaseline  to  relieve  the  excessive  dryness  and  tension. 

On  February  25th,  owing  to  a  positive  Wassermann  reaction, 
an  intravenous  administration  of  salvarsan  was  given  without  any 
appreciable  influence  upon  the  eruption. 

On  January  17th.  the  patient  was  placed  on  a  diet  consisting 
of  an  average  of  27.79  grams  of  nitrogen  and  about  2700  calories 
per  day  (38.7  calories  per  kg.)  The  am6unt  of  nitrogen  retained 
on  the  first  day  of  that  diet  was  9.8  grams.  High  nitrogen  re- 
tention continued  throughout  the  entire  period.  The  total  amount 
of  nitrogen  ingested  during  the  period  (5  days)  was  138.93  grams. 
In  the  urine  and  fa?ces,  104.35  grams  were  eliminated;  21.5  grams  of 
scales  were  collected,  11.12%  of  which  was  nitrogen,  equalling  2.39 
grams  of  nitrogen.  This  leaves  a  net  retention  of  32.19  grams  of 
nitrogen.  The  average  body  weight  was  70.2  kg. 

In  Period  2,  the  patient  was  placed  on  a  diet  consisting  of  an 
average  of  13.45  grams  of  nitrogen  and  an  energy  supply  of  about 
2500  calories  per  day  (36  calories  per  kg.)  During  this  period  the 
patient  ingested  94.12  grams  of  nitrogen.  He  eliminated  82.32 
grams  in  the  urine  and  faeces.  During  the  period,  64.0  grams  of 


PLATE  XXXII. — To  Illustrate  Article  on  Research  Studies  in  Psoriasis, 

bV    DBS.     SCHAMKERG,     KOLMER,     RlNGER     aild     RAIZISS. 


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THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


PLATE  XXXIII. — To  Illustrate  Article  on  Research  Studies  in  Psoriasis, 
by   DHS.   ScirAMitEitG,   KOLMEII,    RINGER   and   RAIZISS. 


THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


RESEARCH    STUDIES    IX    PSORIASIS  81 

scales  were  collected,  containing  7.35  grams  of  nitrogen.  This 
leaves  a  positive  nitrogen  balance  of  4.45  grams.  The  average  body 
weight  was  69.4  kg.,  a  loss  of  0.8  kg. 

In  Period  3,  the  nitrogen  in  the  diet  was  reduced  to  almost  half 
that  of  the  preceding  period,  an  average  of  7.26  grams  per  day 
(0.106  gram  per  kg.).  The  caloric  value  of  the  food  was  about  1600 
per  day  (23.3  calories  per  kg.).  The  change  from  the  high  to  the 
low  diet  was  associated  with  a  negative  nitrogen  balance,  which  lasted 
for  four  days  of  the  period.  During  the  last  three  days,  there  was 
a  positive  balance. 

When  we  consider  the  balance  for  the  week,  we  are  surprised 
to  find  that  the  patient  almost  reached  nitrogenous  equilibrium  on 
this  low  diet.  He  ingested  50.84  grams  of  nitrogen  and  excreted 
51.54  grams,  a  loss  of  only  0.7  gram.  Only  1.5  grams  of  scales 
were  collected  during  .the  period.  The  patient's  average  weight 
was  68.6  kg.,  a  loss  of  0.8  kg. 

The  establishment  of  nitrogenous  equilibrium  on  a  diet  contain- 
ing onty  0.106  gram  of  nitrogen  per  kg.,  and  an  energy  supply  that 
is  a  great  deal  less  than  is  required  for  the  maintenance  of  caloric 
equilibrium  and  which  is  associated  with  considerable  loss  in  body 
weight,  again  show  what  a  remarkable  tenacity  these  patients'  bodies 
have  for  protein. 

In  Period  4,  the  diet  consisted  of  approximately  the  same  amount 
of  nitrogen,  but  of  a  higher  caloric  value — 2100  per  day  (30.8 
calories  per  kg.).  The  amount  of  nitrogen  ingested  was  54.18  grams; 
the  amount  excreted  was  43.16  grams.  7.5  grams  of  scales  were  col- 
lected, but  no  analysis  was  made.  Since  none  of  this  patient's 
scales  were  found  to  contain  more  than  12%  of  nitrogen,  the  7.5 
grams  of  scales  could  not  have  contained  more  than  0.9  gram  of 
nitrogen.  The  net  gain  to  the  body  in 'nitrogen  for  the  period 
was,  therefore,  10.12  grams.  The  patient's  average  weight  was 
68.2  kg.,  a  loss  of  0.4  kg. 

It  is  remarkable  to  note  at  what  a  low  level  of  nitrogen  catabolism 
this  patient  lived.  The  average  elimination  of  nitrogen  in  the 
urine  per  day  was  5.14  grams.  Calculated  per  kg.  of  body  weight, 
we  find  that  only  0.0754  gram  of  nitrogen  was  catabolized  per  kg. 
of  body  weight. 

In  Period  5,  the  patient  received  a  diet  of  about  2600  calories 
and  an  average  of  8.23  grams  of  nitrogen  per  day.  The  total 
amount  of  nitrogen  ingested  was  57.58  grams.  In  the  urine  and 
faeces  were  eliminated  45.13  grams,  giving  a  positive  balance  of 
12.45  grams  of  nitrogen  and  a  gain  of  0.1  kg.  in  weight. 


SCHAMBERG,   KOL.MKK.   RINGKH.  AND  RAI/ISS 


PATIENT  NO.  5.  MR.  B.  PERIOD  I 

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In  Period  6,  the  same  diet  was  continued,  but  of  a  lower  caloric 
value.  The  patient  lost  0.4  kg.  in  body  weight,  but  retained  16.28 
grams  of  nitrogen. 

On    February   25th   the   patient    left    the   hospital. 

SUMMARY  OF  RESULTS  OBTAINED  IN  THE  STUDY  OF  PATIENT  No.  5. 

This  patient,  like  Patients  3  and  4,  possessed  the  ability  to  store 
nitrogen  when  on  a  very  low  protein  diet.  During  the  course  of  his 
stay  in  the  hospital,  the  patient  retained  86.83  grams  of  nitrogen, 
but  lost  2.3  kg.  of  body  weight  (see  table  No.  4,  p.  78). 

PATIENT  No.  8. 
M.  C.;  age  27  years;  female;  born  in  Italy. 

FAMILY  HISTORY.  Her  mother  died  at  the  age  of  64  years,  of  unknown  cause 
and  her  father  at  the  age  of  35,  of  heart  disease.  The  patient  is  unable  to  recall 
any  facts  relating  to  the  history  of  illness  in  her  early  life. 

PREVIOUS  HISTORY.  She  is  married  and  has  had  5  children.  The  first  preg- 
nancy terminated  in  a  miscarriage  at  7  months.  The  second  child  is  living  and 
well  and  has  been  personally  examined  to  verify  this  fact.  The  third  pregnancy 
miscarried  at  five  months.  The  fourth  child  died  when  18  days  old.  The  last 
child  is  living  and  well.  The  patient  had  a  positive  Wassermann  of  moderate 
degree. 

PRESENT  DISEASE.  The  patient  has  suffered  from  psoriasis  for  four  years.  She 
was  admitted  to  the  Polyclinic  Hospital  on  April  22,  1913. 

At  this  time  she  was  suffering  from  a  severe  and  widespread  psoriasis  in- 
volving the  face,  trunk  and  extremities  (Figs.  13  and  15).  The  eruption  covered 
the  greater  part  of  the  face  and  scalp  and  involved,  in  thick  nummular  plaques, 
about  three  quarters  of  the  cutaneous  surface.  A  great  amount  of  scales  was 
thrown  off  every  24  hours:  the  patient  complained  of  painful  dryness,  tension  and 
Assuring,  which  required  the  use  of  vaseline  for  its  relief.  There  were  deep 
fissures  about  the  knees,  elbows  and  finger  joints.  The  fingers  were  held  in  an 
extended  position  and  could  not  be  bent  on  account  of  the  accompanying  pain. 

The  patient  remained  in  the  hospital  49  days  and  was  ^discharged  at  her  re- 
quest on  June  6th,  as  her  presence  at  home  was  demanded. 

This  patient  had  a  most  severe,  inflammatory  and  extensive  erup- 
tion. Seldom  does  one  see  a  more  widespread  eruption,  unless  the 
psoriasis  is  a  diffuse,  universal  one.  The  patient  complained  bit- 
terly of  soreness  of  the  skin  and  pain  from  the  fissures,  particularly 
those  about  the  knees,  elbows  and  fingers.  She  is  very  sensitive  to 
cold. 

The  patient  was  placed  on  a  low  nitrogen  diet  on  April  23rd. 
By  May  1st,  improvement  was  noticed  in  the  skin  and  the  subjective 
symptoms  were  much  relieved.  The  scaling,  which  had  been  very 
profuse,  had  considerably  lessened  by  May  9th.  Vaseline  was  ap- 


PLATE  XXXIV. — To  Illustrate  Article  on  Research  Studies  in  Psoriasis, 
bv  DBS.   SCIIAMBERG,   KoLMER.   RINGER   and   RAIZISS. 


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THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


PLATE   XXXV. — To  Illustrate  Article  on  Re-earch  Studies  in  Psoriasis, 
In    Dus.   SCHAMBERG,   KOLMER,   RINGER   and   RAIZISS. 


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RESEARCH    STUDIES    IN    PSORIASIS  89 

plied  as  infrequently  as  possible,  without  subjecting  the  patient  to 
unnecessary  distress.  A  note  made  on  May  10th,  states  that  "vaseline 
has  not  been  applied  for  three  days."  By  May  10th,  the  skin  over 
the  breasts  and  shoulders  had  become  much  paler. 

By  reference  to  Figs.  13,  14,  15  and  16,  the  improvement  in  the 
eruption  between  April  23rd,  and  May  21st,  (the  dates  of  the  re- 
spective photographs)  is  clearly  seen.  In  view  of  the  fact  that  no 
internal  treatment  whatsoever  was  employed  and  no  local  treatment 
save  the  use  of  vaseline,  the  change,  we  believe,  is  truly  remarkable. 
This  improvement  continued  up  to  the  date  of  her  departure.  After 
discharge  from  the  hospital,  the  patient  was  unable,  owing  to  poverty 
and  other  causes,  to  continue  the  diet  prescribed  and  she  returned  to 
the  hospital  some  weeks  later  with  the  eruption  much  aggravated, 

In  Period  1,  the  patient  was  placed  on  a  diet  consisting  of  an 
average  of  6.84  grams  of  nitrogen  and  1439  calories  per  day.  (22.80 
calories  per  kg.)  During  the  period,  she  ingested  47.90  grams  of 
nitrogen.  She  eliminated  34.62  grams  in  the  urine  and  4.67  grams 
in  the  fsces.  This  leaves  a  positive  balance  of  8.61  grams.  41 
grams  of  scales  were  collected,  containing  4.95  grams  of  nitrogen. 
On  subtracting  this  from  8.61,  we  find  that  on  'this  poor  diet  the 
patient  retained  3.66  grams  of  nitrogen.  The  patient's  average 
weight  was  63.1  kg. 

In  Period  2,  the  patient  was  placed  on  a  diet  lower  than  the 
preceding  one  in  its  caloric  and  nitrogen  content.  It  contained  an 
average  of  6.08  grams  of  nitrogen  and  1150  calories  per  day 
(about  one-half  the  normal  requirements).  The  total  amount  of 
nitrogen  ingested  was  42.55  grams.  The  amount  eliminated  in  the 
urine  and  faces  was  37.85  grams.  65  grams  of  scales  were  collected, 
containing  8.23  grams  of  nitrogen.  This  leaves  a  negative  nitrogen 
balance  of  3.53  grams.  The  patient's  average  weight  was  60.6  kg., 
a  loss  of  2.5  kg. 

In  Period  3,  the  diet  consisted  of  an  average  of  7.08  grams  of 
nitrogen  and  1553  calories  per  day  (26.42  calories  per  kg.).  Dur- 
ing the  period,  49.59  grams  of  nitrogen  were  ingested.  Only  25.26 
grams  were  eliminated  in  the  urine  (3.61  grams  per  day).  6.40 
grams  of  nitrogen  were  found  in  the  faeces  and  11.20  grams  in  the 
scales.  This  results  in  a  net  nitrogen  balance  of  6.73  grams  in  favor 
of  the  body. 

On  May  10th,  500  cc.  of  milk,  containing  2.51  grams  of  nitrogen 
were  added  to  the  patient's  diet.  As  is  seen  from  the  chart,  the 
extra  protein  caused  no  increase  in  the  nitrogen  elimination.  The 
patient's  average  weight  was  58.8  kg.,  a  loss  of  1.8  kg. 


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<)<>       SCHAMBERG,  KOLMER,  RINGER,  AND  RAI/ISS 

In  Period  4,  the  same  amount  of  nitrogen  was  administered  as 
in  Period  3,  but  the  diet  contained  a  higher  caloric  value  (36.5 
calories  per  kg.).  During  the  period,  52.45  grams  of  nitrogen  were 
ingested.  Only  20.89  grams  of  nitrogen  were  eliminated  in  the 
urine,  i.e.,  2.89  grams  per  day.  14.03  grams  of  nitrogen  were 
found  in  the  freces,  and  8.83  grams  in  66.0  grams  of  scales  that  were 
collected  during  the  period.  This  leaves  a  positive  nitrogen  balance 
of  9.3  grams.  The  patient's  average  weight  was  58.5  kg.,  a  loss  of 
0.3  kg. 

On  May  18th,  1000  cc.  of  milk,  containing  5.05  grams  of  nitro- 
gen, were  added  to  the  diet.  In  normal  conditions,  this  would  have 
caused  a  considerable,  if  not  a  corresponding  rise,  in  the  output 
of  urinary  nitrogen.  In  this  case  there  was  no  increase  whatsoever. 
The  significance  of  this  will  be  discussed  later. 

In  Period  5,  approximately  the  same  diet  was  maintained  as  in 
the  preceding  period.  The  period  consisted  of  nine  days,  in  which 
70.21  grains  of  nitrogen  were  ingested.  During  this  period  the 
patient  eliminated  40.57  grams  of  nitrogen  in  the  urine  and  faeces. 
114  grams  of  scales  were  exfoliated,  14.4%  of  which  was  nitrogen, 
equalling  16.42  grams.  This  leaves  a  net  nitrogen  balance  of  13.22 
grams  in  favor  of  the  body.  The  patient's  average  weight  was 
58.15  kg.,  a  loss  of  0.35  kg. 

On  May  22nd,  100  grams  of  sweetbread  were  added  to  the  diet. 
This  meant  an  additional  ingestion  of  3.54  grams  of  nitrogen,  or 
a  total  of  10.65  grams.  The  amount  eliminated  in  the  urine  was 
only  3.40  grams  of  nitrogen,  an  increase  of  less  than  0.7  gram  above 
that  of  the  preceding  and  following  days. 

On  May  27th,  the  patient  was  given  20  grams  of  glycocoll 
(Kahlbaum)  containing  3.74  grams  of  nitrogen.  2.75  grams  of 
extra  nitrogen  appeared  in  the  urine  of  May  27th  and  28th.  All 
of  the  extra  nitrogen  was  eliminated  in  the  form  of  urea.  There 
was  no  increase  in  the  undetermined  nitrogen.  Almost  1  gram  of 
the  glycocoll  nitrogen  was  retained  in  the  system. 

From  the  foregoing,  two  very  significant  facts  stand  out  promi- 
nently. First,  the  very  large  amounts  of  nitrogen  that  may  be  lost 
I  through  the  skin  in  exfoliated  epithelium  (scales)  ;  second,  the  small 
amounts  of  nitrogen  eliminated  in  the  urine.  In  Period  4,  the  daily 
average  of  urinary  nitrogen  amounted  to  2.89  grams;  in  Period  5, 
it  was  2.78  grams  (excluding  May  22nd,  27th  and  28th,  when  spe- 
cial substances  were  fed).  These  are  the  very  lowest  amounts  of 
nitrogen  that  have  ever  been  found  in  the  urine  of  an  individual  of 
that  weight.21  In  Period  6,  we  wished  to  find  out  the  lowest  level 


RESEARCH    STUDIES    IN    PSORIASIS 


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98       SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

that  the  urinary  nitrogen  can  be  reduced  to.  We  therefore  reduced 
the  nitrogen  intake  to  an  average  of  4.39  grams  per  day.  The 
total  nitrogen  intake  for  the  week  was  30.70  grams.  13.78  grams 
of  nitrogen  were  found  in  the  fasces.  The  amount  of  nitrogen  elim- 
inated in  the  urine  sank  to  below  two  grams  per  day.  Only  13.16 
grams  of  nitrogen  were  eliminated  in  the  urine  for  the  period — an 
average  of  1.88  grams  per  day.  74  grams  of  scales  were  collected, 
in  which  were  8.75  grams  of  nitrogen. 

The  nitrogen  balance  for  the  period  was  as  follows : 

Ingested  Excreted  Scales  Balance  Body 

Urine  'Faeces  Weight 

30.70  13.16  13.78  8.75  —4.99  —0.25  kg. 

We  believe  that  this  experiment  throws  a  great  deal  of  light  on 
the  mechanism  of  protein  metabolism  in  patients  with  psoriasis,  and 
we  shall  return  to  this  later. 

At  this  point  we  wished  to  place  the  patient  on  a  nitrogen-free 
diet,  but,  to  our  great  disappointment,  family  affairs  required  her 
immediate  return  to  the  home.  On  June  6th  she  left  the  hospital. 

SUMMARY  OF  RESULTS  OBTAINED  IN  THE  STUDY  or  PATIENT  No.  8 

In  this  patient,  as  in  the  preceding  ones,  a  marked  tendency  to 
nitrogen  retention  was  noted.  The  lowest  figures  for  urinary  nitro- 
gen (1.88  grams  per  day)  were  observed  in  this  case,  when  the 
intake  was  reduced  to  a  little  less  than  4  grams  (table  No.  5,  p. 
97). 

During  the  course  of  the  investigation,  which  lasted  44  days, 
293.4  grams  of  nitrogen  were  ingested.  The  amount  excreted  was 
210.63  grams,  resulting  in  a  positive  balance  of  82.77  grams.  446 
grams  of  scales  were  collected,  in  which  were  58.38  grams  of  nitrogen. 
The  detailed  study  of  this  case  shows  very  clearly  to  what  a  marked 
extent  the  condition  of  the  skin  may  influence  the  urinary  nitrogen 
(see  Period  6  and  page  130). 

PATIENT  No.  9. 
J.   H.;  female;   single;   18  years  of  age. 

FAMILY  HISTORY.  Her  father  was  killed  by  an  accident  six  years  ago,  at  the 
age  of  41 ;  previous  to  the  accident  he  had  always  been  in  good  health.  He  had 
had  psoriasis  on  the  leg,  when  a  young  man,  before  he  was  married.  Her  mother 
living,  aged  45  years,  in  poor  health;  she  complains  of  stomach  trouble;  she 
has  had  rheumatism  for  the  last  three  years ;  she  is  free  from  skin  diseases. 

An  uncle,  the  mother's  brother,  had  psoriasis  seven  years  ago  and  was  treated 
in  the  Jefferson  Hospital  of  Philadelphia.  An  aunt  by  marriage,  had  psoriasis 


PLATE  XXXVI.— To  Illustrate  Article  on  Research  Studies  in  Psoriasis, 
by   DKS.   SCIIAMBERG,   KOI.MER,   RINGER   and   RAIZISS. 


o 

=-'  5? 


THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


99 

in  1912;  the  attack  lasted  five  weeks;  she  was  treated  by  a  specialist  and  has  not 
seen  any  sign  of  the  psoriasis  since  September,  1912.  The  patient  has  three 
brothers  living,  aged,  14,  17,  21,  respectively,  free  from  skin  disease;  one  sister 
is  dead. 

$•  PERSONAL  HISTORY.  The  patient  was  born  in  Roumania;  she  has  resided  for 
the  last  ten  years  in  the  United  States;  she  worked  hard  at  sewing;  her  appetite 
is  poor  and  the  meals  are  irregular.  The  meals  usually  consist  of  two  eggs  daily, 
meat  once  a  day;  one  glass  of  milk  and  one  or  two  slices  of  bread  daily,  cocoa 
occasionally.  No  wines,  tea,  coffee  or  alcoholic  drinks.  The  bowels  were  usually 
constipated  until  she  was  operated  on  for  appendicitis  in  the  German  Hospital, 
in  1912.  The  patient  has  had  measles;  the  date  of  the  attack  is  not  recalled.  Her 
menses  began  at  the  age  of  14.  She  had  erysipelas  in  February,  1913.  She  has 
suffered  from  headaches  since  she  was  nine  years  of  age. 

PRESEXT  ILLXESS.  The  patient  states  that  the  cutaneous  trouble  started  four 
years  ago,  at  the  age  of  15.  She  first  noticed  a  red  scratch  on  the  left  shoulder; 
then  papules  started  on  the  right  shoulder  and  elsewhere.  She  was  treated  in  the 
Jefferson  Hospital  Dispensary  in  1912. 

The  patient  was  admitted  to  the  Polyclinic  Hospital  on  May  12,  1913.  She 
presented  plaques  of  psoriasis  of  varying  size  upon  the  trunk  and  extremities. 
The  plaques  were  not  numerous,  but  were  large  in  diameter  and  considerably 
infiltrated.  An  extensive  psoriatic  belt,  having  almost  the  shape  of  an  abdominal 
binder,  extended  around  the  lower  part  of  the  abdomen;  this  area  of  psoriasis 
was  very  scaly,  thickened  and  elevated  above  the  surrounding  healthy  skin. 
Scattered  plaques  were  present  upon  the  arms  and  legs  (Figs.  17  and  IS). 

Vaseline  was  applied  to  the  eruption  to  relieve  the  distressing  tension  and 
fissuring.  The  eruption  improved,  but  did  not  disappear  by  the  date  of  the  con- 
clusion of  the  metabolic  studies  on  this  patient.  Chrysarobin,  in  ointment  form, 
was  thereupon  applied  with  a  resulting  disappearance  of  the  patches. 

In  Period  I,  the  patient  was  kept  on  a  diet  consisting  of  an 
average  of  6. -I  grams  of  nitrogen  and  1643  calories  per  day  (30.5 
calories  per  kg.).  The  total  amount  of  nitrogen  ingested  during 
the  period  (8  days)  was  56.18  grams.  The  amount  excreted  was 
56.84  grams.  During  the  period,  46.0  grams  of  scales  were  col- 
lected, containing  6.23  grams  of  nitrogen.  The  net  nitrogen  balance 
was,  therefore,  6.89  grams.  The  patient's  average  weight  was 
53.96  kg. 

On  May  18th,  1000  cc.  of  milk,  containing  5.05  grams  of  nitro- 
gen, were  added  to  the  diet.  As  is  seen  from  the  chart  (page  101) 
less  than  one  gram  of  extra  nitrogen  was  eliminated  in  the  urine. 
The  rest  was  retained. 

In  Period  2,  an  average  of  7.04  grams  of  nitrogen  and  2317 
calories  vere  given  per  day.  On  May  22nd,  100  grams  of  sweet- 
bread, containing  3.54  grams  of  nitrogen,  were  added  to  the  diet. 
On  that  day  there  was  an  increase  of  one  gram  in  the  urinary  output 
of  nitrogen.  The  rest  was  retained  in  the  system. 

On  May  27th,  20  grams  of  glycocoll,  containing  3.74  grams  of 
nitrogen,  were  added  to  the  diet.  The  nitrogen  elimination  in  the 
urine  was  3.80  and  3.98  grams  on  the  25th  and  26th  of  May, 


100     SCHAMHKHG,  KOLMKK,  RINGKK,  AND  RAIZISS 

respectively.  It  rose  to  6.00  and  5.95  grams  on  the  27th  and  28th 
of  May,  and  came  down  again  on  the  29th  to  4.12  grams.  There 
were  eliminated  3.67  grams  of  extra  nitrogen,  which  is  almost  quan- 
titative elimination.  A  glance  at  the  column  of  undetermined  nitro- 
gen, however,  reveals  the  fact  that  not  all  the  glycocoll  was  catabol- 
i/ed.  The  undetermined  nitrogen,  which  was  fairly  constant — 0.57 
and  0.53  grams  per  day — rose  to  0.93  and  1.31  on  May  27th  and 
May  28th  respectively,  to  fall  again  to  0.48  gram  on  the  29th  of 
May.  While  all  the  glycocoll  found  its  way  to  the  urine,  only 
2.53  grams  were  eliminated  in  the  form  of  urea  and  1.14  grams 
were  eliminated,  in  all  probability,  unchanged. 

The  total  amount  of  nitrogen  ingested  during  the  period  (9 
days)  was  70.67  grams.  In  the  urine  and  faeces  there  were  elim- 
inated 53.10  grams,  and  in  the  scales  there  were  found  5.27  grams 
of  nitrogen.  The  total  output  amounted  to  58.37  grams,  resulting 
in  a  net  positive  balance  of  12.30  grams.  The  patient's  average 
weight  was  54.53  kg.,  a  gain  of  0.57  kg. 

In  Period  3,  the  nitrogen  intake  was  reduced  to  an  average  of 
4.28  grams  per  day  (for  object  of  this  experiment  see  pages  96, 
98).  The  total  amount  of  nitrogen  ingested  during  the  period  was 
30.04  grams.  The  faeces  of  this  period  was  found  to  contain  13.54 
grams  of  nitrogen.  The  amount  of  nitrogen  eliminated  in  the  urine 
was  20.94  grams,  or  2.99  grams  per  day.  The  nitrogen  excreted  in 
the  urine  and  faeces,  therefore,  exceeded  the  ingested  nitrogen  by  4.44 
grams.  In  the  21  grams  of  scales  collected,  there  were  2.47  grams 
of  nitrogen.  This  results  in  a  net  loss  to  the  body  of  6.91  grams  of 
nitrogen.  The  average  weight  of  the  patient  was  54.6  kg.,  a  gain 
of  0.07  kg.  (Patient  No.  8  was  kept  on  the  same  diet  in  Period  6. 
Note  the  difference  in  results.  See  page  95.) 

In  Period  4,  the  patient  was  kept  on  approximately  the  same 
diet  as  in  Period  3,  but  with  a  higher  amount  of  nitrogen,  namely, 
5.16  grams  per  day.  The  scaling  diminished  considerably  during  this 
period,  so  that  only  2.5  grams  of  scales  were  collected. 

The  total  amount  of  nitrogen  ingested  during  Period  4  was 
36.15  grams.  The  amount  excreted  was  30.47  grams,  leaving  a 
positive  balance  of  5.68  grams.  The  average  weight  of  the  patient 
was  54.54  kg.,  a  loss  of  0.06  kg. 

The  average  amount  of  nitrogen  eliminated  in  the  urine  per  day 
was  2.47  grams.  When  we  consider  this  amount  in  relation  to  the 
patient's  weight,  we  find  that  0.0453  grams  of  nitrogen  were  elim- 
inated in  the  urine  per  kg.  of  body  weight.  The  question  then  pre- 
sented itself,  what  is  the  lowest  amount  of  nitrogen  that  this  patient 


RESEARCH    STUDIES    IN    PSORIASIS 


101 


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ANALYSIS  OF  SCALES  COLLECTED  DURING  PERIOD 
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RESEARCH    STUDIES    IN    PSORIASIS 


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RESEARCH    STUDIES    IN    PSORIASIS 


105 


PATIENT  NO.  9.  MISS  J.  H.  PERIOD  V 

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106     SCHAMBERG,  KOLMER,  RINGER,  AXD  RAIZISS 


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RESEARCH    STUDIES    IN    PSORIASIS 


107 


PATIENT  NO.  9.  MISS  J.  H.  PERIOD  VII 

Calories 

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Eaten 
in  Grams 

ooot- 
oooo 

M  i-l  i-H 

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Potato  cake  
Peaches  
Cornstarch  pudding  .... 
Strawberries  

Total  

1 

•*  10  to  i-H  0  N 
anN**  C-lON 
CONtOIN 

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1        1 

TC  •*  10  00  r)"  O 
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108     SCHAMIiKKG,  KOLMER,  RINGER,  AND  RAIZISS 

would  eliminate,  if  placed  on  a  diet  as  free  from  nitrogen  as  can 
be  conveniently  administered? 

Our  original  intention  was  to  place  the  patient  on  a  diet  con- 
sisting of  carbohydrates  and  fats  and  free  from  nitrogen,  the  carbo- 
hydrates and  fats  in  sufficient  quantity  to  cover  all  the  caloric 
requirements. 

Experiments  of  this  sort  were  first  described  by  Landergren.1'2 
He  hoped  to  show  that  by  keeping  a  man  on  a  diet  containing  suffi- 
cient caloric  value  to  cover  all  the  energy  requirements,  but  in  a 
state  of  specific  nitrogen  hunger,  that  the  lowest  nitrogen  catabolism 
compatible  with  life  will  take  place.  He  found  that  during  the 
first  3  to  5  days  there  was  a  gradual  decline  in  the  nitrogen  output, 
which  reached  the  lowest  level  on  the  4th  to  6th  day,  when  it  re- 
mained constant.  The  nitrogen  eliminated  at  this  time  per  kg.  of 
body  weight  per  24  hours  was  40  to  50  mg. 

We  planned  to  keep  our  patient  on  a  diet  similar  to  Lander- 
gren's,  but  we  soon  had  to  modify  our  plans  on  account  of  the 
monotony  of  the  diet.  The  patient  ate  only  a  small  fraction  of  the 
sago  starch. 

The  experiment  lasted  for  three  days.  On  June  13th,  the  patient 
received  0.87  gram  of  nitrogen  in  the  food  which  had  a  heat  value 
of  651  calories.  On  this  day  the  patient  eliminated  2.5  grams  of 
nitrogen  in  the  urine.  On  June  14th,  0.26  gram  of  nitrogen  was 
ingested  in  the  food,  which  had  a  heat  value  of  only  440  calories. 
On  this  day  1.65  grams  of  nitrogen  were  eliminated  in  the  urine. 
On  June  15th,  0.32  gram  of  nitrogen  was  ingested  in  the  food 
which  had  a  heat  value  of  611  calories.  The  amount  of  nitrogen 
in  the  urine  was  1.67  grams.  At  this  point  we  were  forced  to 
abandon  the  diet  because  of  its  monotony. 

While  the  experiment  was  not  as  complete  as  originally  planned, 
it  nevertheless  possesses  considerable  significance :  on  the  second  day 
of  this  diet  the  urinary  nitrogen  seems  to  have  struck  a  level  below 
which  it  did  not  go  down.  From  the  experiments  of  Landergren 
and  others,  we  know  that  it  takes  at  least  three  days  to  reach  the 
lowest  level  of  nitrogen  catabolism.  Our  patient  struck  that  level 
on  the  second  day  of  the  experiment.  The  amount  of  nitrogen 
eliminated  in  the  urine  per  kg.  of  body  weight  was  0.0311  gram, 
showing  to  what  an  extent  the  patient's  tissues  were  depleted  of  their 
reserve  protein  (see  table  No.  6,  p.  97). 


RESEARCH    STUDIES    IN    PSORIASIS  109 

PATIENT  No.  7. 
R.  A.;  male;  age,  16;  born  in  Russia. 

FAMILY  HISTORY.  His  father  is  living  at  the  age  of  42  years.  He  is  in  good 
health.  He  had  catarrn  of  the  stomach  for  ten  years.  He  has  never  had  any  skin 
disease.  His  mother  is  living  and  well  at  the  age  of  42  years;  she  had  an  attack 
of  rheumatism  this  winter  (1913).  She  has  been  always  free  from  skin  disease. 

He  has  two  brothers  aged  12  and  18  years,  respectively,  and  one  sister,  aged 
8  years,  who  is  in  good  health.  Two  brothers  died  in  infancy;  cause  unknown. 
The  brothers  and  sister  are  free  from  skin  disease. 

PERSONAL  HISTORY.  The  patient  has  resided  in  Philadelphia  for  the  last  five 
years.  He  has  worked  quite  hard  in  an  upholstery  factory.  His  appetite  is  good; 
he  is  well  nourished;  he  is  a  moderate  tea  drinker.  He  has  never  indulged  in 
alcoholic  drinks  or  in  coffee.  He  is  very  nervous;  he  had  chorea  in  1912.  Always 
slept  well  until  he  had  the  attack  of  chorea,  when  he  was  very  restless;  he  still 
shows  signs  of  the  muscular  twitching  of  the  face,  back,  arms  and  abdomen.  He 
had  rheumatism  at  the  age  of  14,  and  measles  when  2  years  old. 

PRESENT  ILLNESS.  He  states  that  he  was  in  Jefferson  Hospital  for  treatment 
for  chorea  in  March  and  one  month  after  admission  to  the  Hospital,  he  noticed  a 
red  spot  on  the  cheek  (in  the  latter  part  of  April).  This  was  followed  by  a  more 
or  less  generalized  eruption.  The  psoriasis  first  appeared  while  the  patient  was 
taking  arsenic  for  his  chorea.  He  was  free  from  psoriasis  for  two  and  a  half 
months  during  October,  November  and  part  of  December.  A  second  attack  of 
psoriasis  began  in  January,  papules  appearing  on  the  forehead,  then  upon  the 
body,  legs,  arms  and  face.  The  patient  states  that  during  the  first  year,  the 
eruption  was  most  pronounced  in  July  and  August.  He  was  admitted  to  the 
Polyclinic  Hospital  on  April  8,  1913.  On  admission,  the  patient  presented  a 
number  of  psoriasis  plaques  from  2  to  4  cm.  in  diameter,  scattered  over  the  trunk 
and  extremities;  the  eruption  was  only  moderate  in  extent.  There  were  numerous 
areas  of  brownish  pigmentation  at  the  site  of  previous  psoriasis  areas;  the  face  was 
quite  covered  with  psoriasis  scales. 

A  neurological  examination  made  by  Dr.  John  Rhein,  yielded  the  following 
results: 

No  subjective  sensory  phenomena — outside  of  some  itching.  Station  good. 
Knee  jerks  slightly  +  and  equal.  Babinski  absent.  Plantar  reflex  normal. 
Abdominal  reflex  normal.  Cremasteric  reflex  normal.  Slight  irregular  tremor  of 
both  arms  and  hands,  slightly  increased  on  voluntary  effort.  No  change  in  sensa- 
tion. Some  mild  general  choreiform  movements  present.  Coordinates  the  hands 
well.  Pupils  react  normally;  they  are  equal.  No  ocular  palsies.  Some  rotary 
and  lateral  nystagmus. 

In  the  study  of  all  the  cases  cited  above,  a  very  marked  and 
decided  improvement  was  noted  after  the  patient  had  been  kept  on 
a  low  protein  diet.  In  all  of  our  cases,  all  medicinal  treatments, 
internal  as  well  as  external,  were  omitted.  There  remained  only 
two  factors  which  might  have  influenced  the  course  of  the  psoriasis 
in  our  patients.  First,  the  sojourn  in  the  hospital,  with  its  hygienic 
environment  and,  secondly,  the  regime  of  the  low  protein  diet.  We 
therefore  decided  to  keep  Patient  No.  7  on  a  high  protein  diet,  vary- 
ing from  period  to  period  between  23.7  grams  of  nitrogen  per  day, 
to  38.65  grams  of  nitrogen  per  day.  Our  object  was  to  discover 


110     SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 


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RESEARCH    STUDIES    IX    PSORIASIS 


111 


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Eaten 
in  Grams 

10 

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112     SCHAMBERG,  KOLMKK,  UINGKH,  AND  RAIZISS 


PATIENT  NO.  7.  MR.  AB.  PERIOD  III 

1 

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50  CO  00  to  10  •-(  O> 

*  : 

«     ; 

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Calories  per  kg.  of  body  weight  
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Nitrogen  in  urine  
Nitrogen  in  feces  
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RESEARCH    STUDIES    IN    PSORIASIS 


113 


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114-     SCHAMBKRG,  KOLMKll,  RINGER,  AND  RAIZISS 


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RESEARCH    STUDIES    IN    PSORIASIS 


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118     SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

to  what  extent  the  sojourn  in  the  hospital  alone  influenced  the 
course  of  the  psoriasis. 

In  Period  1,  the  patient  was  placed  on  a  diet  consisting  of  an 
average  of  24.89  grams  of  nitrogen  per  day.  The  heat  value  of 
the  food  was  about  2600  calories  per  day,  or  47.8  calories  per  kg. 
The  total  amount  of  nitrogen  ingested  during  the  period  (12  days) 
was  298.64  grams.  The  amount  excreted  was  244.48  grams,  result- 
ing in  a  positive  balance  of  54.16  grams  of  nitrogen.  The  average 
body  weight  was  54.9  kg. 

In  Period  2,  approximately  the  same  diet  was  continued.  During 
the  period  (10  days)  237.11  grams  of  nitrogen  were  ingested  and 
208.38  grams  were  excreted,  leaving  a  positive  nitrogen  balance 
of  28.73  grams.  The  average  body  weight  was  55.4  kg.,  a  gain  of 
0.5  kg. 

In  Period  3  (7  days),  the  nitrogen  intake  was  raised  to  an 
average  of  30.59  grams  per  day.  The  total  amount  ingested  dur- 
ing the  period  was  214.10  grams.  The  amount  excreted  was  177.77 
grams,  leaving  a  positive  balance  of  36.33  grams.  The  caloric 
value  of  the  food  was  about  2900  calories  per  day,  or  52.7  calories 
per  kg.  The  patient's  average  weight  was  55.3  kg.,  a  loss  of  0.10  kg. 

In  Period  4,  the  average  nitrogen  intake  was  27.36  grams.  Dur- 
ing the  course  of  the  period  (9  days)  246.27  grams  of  nitrogen 
were  ingested.  The  amount  eliminated  in  the  urine  and  faeces  was 
210.77  grams,  leaving  a  positive  balance  of  35.50  grams.  The 
average  weight  of  the  patient  was  55.7  kg.,  a  gain  of  0.4  kg. 

In  Period  5,  the  nitrogen  intake  was  raised  to  an  average  of 
38.65  grams  per  day.  The  total  amount  ingested  during  the  period 
(7  days)  was  270.58  grams.  In  the  urine  and  faeces  were  eliminated 
218.43  grams,  which  leaves  a  positive  balance  of  52.15  grams.  The 
patient's  average  weight  was  56.5  kg.,  a  gain  of  0.8  kg. 

In  Period  6,  an  average  of  26.09  grams  was  ingested  per  day. 
The  total  amount  for  the  period  was  182.66  grams.  The  amount 
excreted  was  143.98  grams,  leaving  a  positive  balance  of  38.68 
grams.  The  patient's  average  weight  was  56.3  kg.,  a  loss  of 
0.20  kg. 

In  Period  7,  197.90  grams  of  nitrogen  were  ingested,  *.  e.,  an 
average  of  28.27  grams  per  day.  The  amount  eliminated  in  the  urine 
and  faeces  was  157.10  grams,  leaving  a  positive  balance  of  40.80 
grams  (see  table  No.  7,  p.  119). 

This  case  has  a  special  interest,  inasmuch  as  the  patient  was 
used  partly  as  a  clinical  control  for  the  other  patients.  In  order 
to  determine  whether  psoriasis  would  improve  as  a  result  of  the 


PLATE  XXXVII.— To  Illustrate  Article  on   Research  Studies  in  Psoriasis, 
bv   DBS.   SCIIAMBERG,   Koi.MER.    RINGER   and   RAIZISS. 


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THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


PLATE  XXXVIII. — To  Illustrate  Article  on  Research  Studies  in  Psoriasis, 
bv  DKS.   SCIIAMBEHG,   KOI.MER,   RINGER   and   RAIZISS. 


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RESEARCH    STUDIES    IN    PSORIASIS 


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Hirschfeld  I  (1888)  .  . 
II  (1888)  .  . 
Klemperer  I  (1889)  .  . 
'*  II  (1889).. 
Siven,  1901  
Patient  No.  8  per  VI 
Patient  No.  9  per  III 
Patient  No.  9  per  IV 

120     SCIIAMBKRG,  KOLMKR,  RINGKR,  AND  RAIZISS 

physical  and  mental  rest  incident  to  sojourn  in  a  hospital,  irre- 
spective of  the  character  of  the  diet,  the  patient  was  not  placed 
on  a  low  nitrogen  dietary,  but,  on  the  contrary,  was  given  a  high 
nitrogen  intake.  After  a  few  weeks'  residence  in  the  hospital,  there 
was  a  pronounced  improvement  in  the  patient's  nervous  condition ; 
the  choreiform  movements  were  distinctly  less  marked.  No  improve- 
ment, however,  took  place  in  the  psoriatic  eruption.  Indeed,  under 
this  high  nitrogen  diet,  the  psoriasis  plaques  gradually  increased  in 
size  and  some  new  patches  appeared.  After  a  number  of  weeks, 
many  of  the  patches  began  to  clear  in  the  centre  and  became  cir- 
cinate.  The  patient  remained  in  the  hospital  from  April  8th  to 
July  1st,  a  period  of  84  days,  and  at  the  end  of  this  time  the 
psoriasis  was  worse  than  upon  admission.  The  relative  appearance 
of  the  eruption  on  April  10th  and  on  May  21st  is  seen  in  Figs.  19, 
20,  21  and  22.  The  increase  in  the  size  of  the  patches  was  verified 
by  actual  measurement. 

Before  discharge  from  the  hospital,  a  chrysarobin  ointment  was 
applied  and  the  eruption  gradually  disappeared. 

DISCUSSION  OF  RESULTS. 

From  the  study  of  the  cases  presented  above,  the  following  con- 
clusions may  be  drawn: 

1.  That    these    patients    possess    a    strong    tendency    to    store 
nitrogen. 

2.  That  the  nitrogen  is  stored  with  great  ease. 

3.  That  on  a  low  protein  diet  the  patients  may  eliminate  extraor- 
dinarily small  quantities  of  nitrogen  in  their  urine. 

4.  That  a  low  protein   diet  has   a  distinct   and  a   remarkably 
beneficial  influence  on  the  course  of  the  psoriasis. 

5.  That  very  large  quantities  of  nitrogen  may  be  lost  through 
the  skin  in  the  form  of  scales. 

6.  That  on  a  high  protein  diet  tremendous  quantities  of  nitro- 
gen may  be  retained  in  the  system. 

7.  That  a  high  protein  diet,  although  it  did  not  bring  about 
a  relapse  in  a  case  where  the  active  process  had  been  checked  (Pa- 
tient No.  3,  Period  15),  did  stimulate  very  considerably  the  course 
of  the  existing  psoriasis  in  active  form.     (Patient  3,  Periods  7  and 
8;  Patient  5,  Period  1,  and  Patient  7.) 

8.  That  the  retention  of  nitrogen  is  not  always  associated  with 
a  coi  responding  gain  in  body  weight. 


RESEARCH    STUDIES    IN    PSORIASIS  121 

For  the  sake  of  convenience,  we  shall  divide  the  discussion  of 
our  results  into  several  chapters : 

THE  VALUE  OP  THE  ELIMINATED  NITROGEN  IN  THE  INTERPRETATION 
OF  PROCESSES  OF  METABOLISM. 

In  the  ordinary  studies  of  protein  metabolism,  two  kinds  of 
nitrogenous  end  products  are  taken  into  consideration. 

1.  URINARY  NITROGEN. — This  represents  the  amount  of  nitrogen 
eliminated   as   urea,    ammonia,   creatinine,   uric   acid,  purin   bodies 
and  other  individually  undeterminable  nitrogenous  compounds,  which 
may  consist  of  amino-acids  and  peptides,  which  managed  to  filter 
through  the  kidney  before  they  were  completely  catabolized.     All 
these  are  cleavage  and  end  products  of  protein  metabolism. 

2.  F.ECAL  NITROGEN. — The  fascal  nitrogen  consists  of  two  frac- 
tions: (1)   nitrogen  secreted  and  excreted  in  the  form  of  ferments 
and  otherwise  by  the  epithelial  cells   of  the  mucous  membrane  of 
the  intestinal  tract,  which  may  be  considered  a  true  product  of  cell 
metabolism  of  the  intestinal  wall  and  (2)  nitrogen  of  the  unresorbed 
food,  which  has  never  played  any  part  in  the  body  metabolism. 

In  some  experiments  the  nitrogen  of  the  perspiration  and  nor- 
mal skin  exfoliation  is  also  taken  into  consideration.  Their  values, 
however,  are  so  small  that  for  all  practical  purposes  they  may  be 
neglected. 

In  the  introductory  chapter  it  was  stated  that  for  the  estima- 
tion of  the  protein  that  is  catabolized  by  an  individual,  it  is  necessary 
to  determine  the  amount  of  nitrogen  eliminated  in  the  urine  and 
faeces  and  to  multiply  that  figure  by  6.25,  which  is  the  ratio  between 
nitrogen  and  protein.  It  is  evident  that  while  this  method  permits 
of  a  very  accurate  study  of  the  nitrogen  and  protein  balances,  our 
inability  to  distinguish  and  separate  the  two  fractions  of  faecal 
nitrogen,  may  cause  the  introduction  of  considerable  error  in  the 
study  of  the  Quantity  of  protein  that  is  actually  catabolized  by 
.the  cells  of  the  body.  The  reader  will,  therefore,  always  bear  in 
mind  that  the  actual  nitrogen  metabolism  of  the  cells  of  the  body 
is  less  than  is  expressed  by  the  sum  of  urinary  and  faecal  nitrogen, 
or  in  other  werds,  the  nitrogen  of  the  food  that  is  resorbed  and 
takes  part  in  the  cell  metabolism  is  less- than  the  amount  ingested. 

In  the  study  of  the  cases  presented  above,  a  third  and  very 
important  factor  of  nitrogen  has  to  be  taken  into  consideration, 
namely,  the  nitrogen  found  in  the  scales  of  the  skin.  Analysis  of 
the  scales  has  shown  that  they  contain  from  9.92  to  14.4%  of  nitro- 


122     SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

gen.  They  also  contain  sulphur  and  phosphorus  and  we  have  every 
reason  to  believe  that  they  consist  primarily  of  protein.  This  being 
the  case,  we  must  include  the  nitrogen  thus  eliminated  in  the  calcu- 
lation of  our  balances,  but  we  must  not  include  that  nitrogen  in 
the  calculation  of  the  body  protein  catabolism.  This  nitrogen  has 
its  own  history  in  the  body  economy  and,  as  will  be  shown  later, 
exerts  a  tremendous  influence  on  the  metabolism  of  the  psoriatic 
patient. 

THE  MINIMAL  PKOTEIN  REQUIREMENTS  AND  THE  MINIMAL  PKOTEIN 

CATABOLISM. 

By  "minimal  protein  requirements"  we  mean  the  smallest  amount 
of  protein  that  is  necessary  to  maintain  an  individual  in  a  state  of 
nitrogenous  equilibrium  and  in  a  normal  degree  of  efficiency.  In 
this  discussion  we  are  not  so  much  interested  in  the  lowest  quantity 
of  protein  that  is  necessary  to  keep  the  body  in  nitrogenous  equilib- 
rium, as  in  the  question:  what  is  the  lowest  quantity  of  protein 
(nitrogen)  per  kg.  of  body  weight  which  has  been  found  to  be 
catabolized  by  human  individuals  under  different  conditions  of 
nutrition. 

We  shall  present  a  brief  resume  of  those  experiments  and  com- 
pare them  with  our  own  observations  on  the  patients  with  psoriasis, 
and  we  thereby  hope  to  be  able  to  throw  some  light  on  the  patholog- 
ical physiology  of  the  protein  metabolism  of  those  patients.  For 
obvious  reasons  we  shall  limit  our  review  to  those  experiments  that 
were  performed  on  man  (see  table  No.  8,  p.  119). 

Hirschfeld  23  was  the  first  to  attempt  a  systematic  study  on  the 
influence  of  low  protein  diets  on  the  urinary  and  fascal  nitrogen 
eliminations.  His  object  was  to  discover  the  lowest  protein  require- 
ments for  nitrogenous  equilibrium.  The  most  important  features  of 
his  experiments  are  tabulated  in  Table  8.  The  experiments  were 
performed  on  a  man  weighing  73  kg.,  and  they  consisted  of  two 
series  of  8  days  each.  In  the  first  series,  the  diet  contained  an 
average  of  4.15  grams  of  nitrogen  per  day  and  an  energy  supply 
of  2852  calories  (39  calories  per  kg.).  The  amount  of  nitrogen 
eliminated  in  the  urine  was  4.74  grams  per  day  and  in  the  fseces 
1.28  grams  per  day,  giving- a  total  of  6.02  grams,  resulting  in  a 
negative  nitrogen  balance  of  1.87  grams  per  day,  i.  e.,,the  amount, 
4.15  grams,  that  was  given  in  the  food  was  not  sufficient  to  cover 
all  the  body's  needs.  In  the  second  series,  therefore,  the  nitrogen 
intake  was  raised  to  an  average  of  7.46  grams  per  day.  Unfor- 


RESEARCH    STUDIES    IN    PSORIASIS  123 

tunately,  a  second  factor  was  introduced  into  this  series  which  no 
doubt  influenced  the  result — the  caloric  value  of  the  food  was  raised 
to  3462  calories  per  day  (47  calories  per  kg.).  Hirschfeld's  point 
would  have  been  brought  out  much  more  clearly  had  the  rise  in  the 
nitrogen  intake  been  the  only  variable.  The  nitrogen  output  in  the 
urine  for  this  period  was  5.76  grams  and  in  the  faeces  1.65  grams, 
making  a  total  of  7.41  grams,  which,  for  all  practical  purposes, 
may  be  considered  the  establishment  of  nitrogenous  equilibrium. 

Simultaneously  with  Hirschfeld,  Klemperer  24  studied  the  ques- 
tion of  the  extent  to  which  the  protein  metabolism  can  be  depressed 
in  normal,  healthy,  human  individuals.  For  a  period  of  8  days, 
he  kept  two  normal  men  on  a  diet  containing  5.28  grams  of  nitrogen 
and  a  heat  value  of  5020  calories  (79.4  calories  per  kg.  in  the  first 
experiment  and  77.4  calories  per  kg.  in  the  second  experiment). 
The  nitrogen  eliminated  in  the  urine  of  the  first  subject,  during  the 
last  three  days  of  the  experiment,  was  3.33  grams  and  in  the  faeces, 
1.26  grams.  The  total  amount  of  nitrogen  eliminated  was  4.59 
grams,  resulting  in  a  positive  nitrogen  balance  of  0.69  gram  per 
day.  In  the  second  subject,  the  urine  contained,  during  the  last 
three  days,  an  average  of  2.87  grams  of  nitrogen  per  day;  the 
fseces  contained  1.02  grams,  giving  a  total  excretion  of  3.89  grsms 
and  a  positive  balance  of  1.39  grams  per  day. 

A  very  interesting  series  of  experiments  was  carried  out  by 
Siven  on  himself,25  which  illustrates  very  clearly  the  relationship 
that  ordinarily  obtains  between  the  nitrogen  of  the  food  and  that 
of  the  urine.  The  heat  value  of  his  food  was  over  40  calories  per 
kg.  of  body  weight. 

Series  1.  2.  3.  4.  5. 

Nitrogen  intake 12.69          10.35          8.71          6.26          4.52 

Output  in  urine 9.44  7.53         6.13         4.62         3.40 

From  the  summary  of  his  results,  as  presented  above,  we  see 
how  closely  the  curve  of  the  latter  follows  that  of  the  former. 

These  experiments  of  Hirschfeld,  Klemperer  and  Siven  are  typ- 
ical ones  and  are  selected  from  among  a  great  many.  They  are 
brought  in  at  this  point  to  illustrate  the  following  facts: 

1.  That  a  normal  individual,  on  a  diet  containing  a  caloric  sup- 
ply sufficient  for  the  maintenance  of  body  functions  (39  calories 
per  kg.),  and  containing  an  amount  of  nitrogen  equivalent  to  0.057 
gram  per  kg.  of  body  weight,  is  not  sufficient  for  the  maintenance 
of  nitrogenous  equilibrium.  The  urinary  nitrogen  calculated  per 
kg.  of  body  weight  was  0.065  gram  per  day  (Hirschfeld  1). 


.124     SCIIAMBKllG,  KOLMKK,  KINGKK,  AND  KAIXISS 

2.  That  the  same  individual,  on  a  diet  having  a  heat  value  of 
47   kg.   per  body  weight  and  0.102  gram   of  nitrogen   per  kg.   of 
body  weight,  did  maintain  nitrogenous  equilibrium.     The  urinary 
nitrogen   calculated  per  kg.   of  body   weight  was  0.079   gram   per 
day  (Hirschfeld  2). 

3.  That    by   doubling   the    caloric    value    of   the    food,    protein 
catabolism  can  be  so  greatly  reduced  that  the  administration   of 
0.083  gram  of  nitrogen  per  kg.  of  body  weight  will  not  only  be 
sufficient  to  cover  the  cells'  needs,  but  will  also  be  associated  with 
a  positive  nitrogen  balance.     The  urinary  nitrogen  in  those  cases 
was   reduced   to   0.052   and   0.044   gram   per  kg.    of  body   weight 
(Klemperer  1  and  2). 

4.  That  on  a  constant  and  sufficient  caloric  supply  the  gradual 
lowering  of  the  nitrogen  in  the  food  is  accompanied  by  a  gradual 
decline  in  the  nitrogen  output ;  the  difference  between  the  two  grad- 
ually diminishes  as  we  go  down  the  scale  (Siven). 

When  we  come  to  examine  the  results  of  our  experiments  in  the 
light  of  the  conclusions  drawn  from  Hirschfeld's,  Klemperer's  and 
Siven's  experiments,  we  note  a  very  remarkable  deviation.  Through- 
out all  our  studies  we  notice  a  marked  and  continuous  disproportion 
existing  between  the  food  nitrogen  and  the  urinary  nitrogen.  The 
urinary  nitrogen  is  always  much  lower  than  is  the  nitrogen  of  a 
normal  individual  on  the  same  diet.  In  Period  6,  Patient  8  received 
0.075  gram  of  nitrogen  per  kg.  of  body  weight.  The  heat  value 
of  the  food  was  only  32  calories  per  kg.  The  average  amount  of 
nitrogen  eliminated  during  the  period  of  seven  days  was  0.032  gram 
per  kg.  of  body  weight.  It  took  over  77  calories  per  kg.  in  Klem- 
perer's  experiments  to  reduce  the  urinary  nitrogen  of  a  normal  in- 
dividual to  0.044  gram,  per  kg.,  while  a  psoriatic  patient  eliminated 
less  nitrogen  on  a  diet  less  than  one-half  tlie  caloric  value  of  Klem- 
perer's  patient. 

The  same  experiment  was  carried  out  in  Patient  9,  Period  3, 
in  which  she  received  0.079  gram  of  nitrogen  and  28.5  calories 
per  kg.  of  body  weight.  The  urinary  nitrogen  was  0.055  gram 
per  kg. 

When  compared  with  Siven's  figures  (page  123)  the  results  ob- 
tained with  Patient  3  are  very  striking. 

Periods.  7.  3.  4.  6. 

Calories  per  kg 53.6  38.00         38.00         42.00 

Nitrogen  intake   20.54          11.93  6.89  6.89 

Nitrogen  in  urine 8.23  6.32  3.90  3.30 


RESEARCH    STUDIES    IN    PSORIASIS  125 

All  this  shows  very  plainly  that  on  a  given  diet,  a  psoriatic 
patient  eliminates  less  nitrogen  in  the  urine  and  that  it  takes  a  much 
less  energy  supply  in  the  -form  of  food  to  keep  the  urinary  nitrogen 
at  a  low  level  than  it  does  in  a  normal  individual. 

This  problem  is  so  intimately  related  to  the  question  of  nitrogen 
retention  that  we  shall  now  proceed  to  a  discussion  of  the  latter 
subject. 

NITROGEN  RETENTION. 

Closely  associated  with  the  condition  of  lowered  nitrogen  elim- 
ination in  the  urine  we  find  a  high  degree  of  nitrogen  retention. 
This  retention  is  evident  in  Patient  No.  3  throughout  her  entire 
stay  of  128  days  in  the  hospital.  The  nitrogen  in  the  food  was 
492  grams  in  excess  of  that  eliminated  in  the  urine  and  faeces.  Aftei1 
subtracting  89.6  grams  of  nitrogen  eliminated  by  the  skin  (see  page 
48),  the  remains  a  net  positive  balance  of  402  grams.  A  care- 
ful perusal  of  the  columns  of  nitrogen  balances  and  nitrogen  in 
the  food,  reveals  a  great  many  interesting  facts,  the  most  important 
of  which  we  consider  the  remarkable  sinking  of  the  urinary  nitrogen 
with  any  reduction  in  the  food  nitrogen.  . 

Patient  No.  4  lived  in  the  hospital  for  42  days  and  she  retained 
129  grams  of  nitrogen  during  this  period;  Patient  No.  5  retained 
86  grams  in  40  days.  Patient  No.  7  was  kept  on  a  high  protein 
diet  throughout  his  stay  in  the  hospital  (59  days)  and  in  this 
period  he  retained  286  grams  erf  nitrogen.  The  quantities  of  nitro- 
gen retained  do  not  present  as  remarkable  a  feature  as  do  the  con- 
ditions under  which  positive  nitrogen  balances  have  been  maintained. 
From  a  careful  study  of  the  conditions  in  which  nitrogen  is  retained 
normally,  we  are  forced  to  some  definite  conclusions  which  seem  to 
explain  the  very  marked  nitrogenous  retentions  in  psoriasis. 

NITROGEN  RETENTION  IN  NORMAL  ADULT  INDIVIDUALS. 

Reference  has  already  been  made  (page  35)  to  the  statement 
that  if  the  quantity  of  protein  intake,  in  an  individual  who  main- 
tains nitrogenous  equilibrium,  is  steadily  increased,  the  nitrogen 
elimination  (catabolism)  of  that  individual  will  increase  correspond- 
ingly, until  an  equilibrium  is  struck  on  a  higher  level.  Under  these 
conditions  the  animal  body  shows  a,  remarkable  stubbornness  in  re- 
fusing to  store  or  retain  any  of  the  ingested  nitrogen.  To  quote 
Pfliiger,  who  has  done  an  enormous  amount  of  work  on  this  subject: 
"Ganz  wunderbar  und  ratselhaft  ist  die  ungeheure  Anstrengung, 


12<>     SCHAMliKUG,  KOLMER,  RINGER,  AND  RAIZISS 

welche  der  Korper  niacht,  um  das  wertvolle  iiberschiissige  Eiweiss, 
moglichst  vollstiindig  zu  zerstoren." 

Bischoff  and  Voit  20  were  the  first  to  discover  that  the  non- 
nitrogenous  food  stuffs  have  a  marked  sparing  influence  on  protein 
catabolism.  The  question  then  naturally  arose:  if  the  body  tends 
so  very  strongly  to  the  establishment  of  nitrogenous  equilibrium 
by  raising  the  catabolism  to  equal  the  intake  and  if  the  giving  of 
a  high  caloric  diet  in  the  form  of  carbohydrates  and  fats  tends  to 
depress  the  catabolism  of  the  protein,  the  intake  remaining  the 
same,  then  there  must,  judged  from  a  priori  reasoning,  follow  a 
storing  of  nitrogen  in  the  body.  If  so,  to  what  extent,  and  in  what 
form?  These  questions  were  raised  by  von  Noorden,27  and  Krug,28 
working  under  his  direction,  attempted  to  find  an  answer  to  them. 
Krug  was  a  young  man  weighing  59  kg.  He  placed  himself  on  a 
diet  consisting  of  2590  calories  (44  calories  per  kg.)  and  for  6 
days  maintained  nitrogenous  equilibrium  on  a  level  of  14.8  grams. 
Then  for  a  period  of  15  days  he  increased  his  food  by  1700  calories, 
making  a  total  of  4290  calories  per  day  (71  calories  per  kg.)  and 
remained  on  approximately  the  same  amount  of  nitrogen  as  before 
(15.4  grams).  This  tremendous  excess  of  food — carbohydrate  and 
fat — cannot  be  burnt  unless  there  is  a  demand  for  it  by  greatly 
increasing  the  activity  of  the  body,  for,  as  von  Noorden  expresses 
it,  "Luxus-consumption  giebt  es  nicht."  There  takes  place,  there- 
fore, a  storing  of  all  the  extra  material  in  the  form  of  glycogen 
and  of  fat,  principally  fat.  Associated  with  this  storing  of  mate- 
rial, there  is  also  a  "tying-up"  of  nitrogenous  material,  a  "laying- 
on"  of  protein,  which  manifests  itself  in  a  positive  nitrogen  balance, 
i.  e.t  a  deficit  of  nitrogen  in  the  urine  and  faeces.  In  Krug's  experi- 
ment there  was  a  diminution  in  the  nitrogen  output  to  the  extent 
of  3.3  grams  per  day,  totaling  for  the  15  days  49.5  grams  of  nitro- 
gen =  309  grams  of  pure  protein. 

There  are  two  facts  in  this  experiment  which  we  wish  to  empha- 
size and  to  bring  clearly  to  the  reader's  mind: 

1.  The  tremendous  energy  supply  (71  calories  per  kg.,  or  double 
the  normal   requirements)    that  was   necessary   to  bring  about  a 
sparing  of  3.3  grams  of  nitrogen  per  day. 

2.  The  relatively  small  amount  of  protein  that  was  retained, 
compared   with   the   total    retention   of   non-nitrogenous   materials. 
Von  Noorden  calculates  that  Krug  stored  2606  grams  of  fat  during 
this  period  and  only  309  grams  of  protein. 

This  experiment  is  so  convincing  that  we  need  not  present  any 
additional  data  for  the  demonstration  of  the  point  that,  while  in 


RESEARCH    STUDIES    IN    PSORIASIS  127 

a  full-grown,  healthy  adult,  a  retention  of  protein  is  possible,  it 
can  be  accomplished  only  by  a  tremendous  amount  of  "pressure" 
in  the  form  of  a  high  supply  of  potential  energy  in  the  food,  much 
in  excess  of  the  requirements — an  amount  clearly  bordering  on  the 
physiological  limits  of  one's  ingestive  capacities.  It  is  impossible 
to  conceive  of  any  prolonged  storing  of  protein  in  healthy  indi- 
viduals, because  it  is  impossible  to  conceive  of  a  prolonged  con- 
tinuance of  such  high  ingestion  of  food,  without  ultimately  result- 
ing in  the  rebellion  of  the  digestive  and  resorptive  apparatus.29 

NITROGEN  RETENTION  JN  GROWING  AND  CONVALESCENT  INDIVIDUALS. 

When  we  turn  our  attention  to  nitrogen  retentions  in  the  grow- 
ing child,  or  in  convalescents,  an  entirely  different  picture  presents 
itself.  From  the  works  of  Rubner  and  his  collaborators,30  it  is 
apparent  that  the  growing  child  retains  nitrogen  with  remarkable 
ease,  even  though  the  caloric  and  protein  supply  of  the  food  is 
but  slightly  above  the  lowest  requirements — wear  and  tear  quota. 
Nay,  nitrogen  retention  takes  place  in  the  growing  child  even  on 
a  diet  insufficient  to  cover  the  heat  loss.  They,  therefore,  draw  the 
conclusion  that  in  the  growing  child  (contrary  to  the  adult)  the 
power  of  nitrogen  retention  is  not  determined  by  the  amount  of 
nitrogenous  and  non-nitrogenous  food,  but  by  the  "growth  impulse" 
(  "Wachstumstrieb") . 

The  observations  made  on  the  convalescent  patient  with  regard 
to  his  ability  to  store  nitrogen,  are  very  similar  to  those  made  on 
a  growing  child.  A  great  many  experiments  have  been  performed 
by  different  investigators  which  prove  this  point.  We  shall  here 
report  a  few  of  the  most  interesting. 

Friedrich  Miiller81  had  the  opportunity  of  studying  the  metab- 
olism of  a  19-year-old  girl,  who  suffered  from  cesophageal  stenosis, 
as  a  result  of  swallowing  caustic  soda  with  suicidal  intent.  For  a 
period  of  8  days  (about  a  month  after  the  accident)  she  could  par- 
take of  no  food.  During  the  last  four  days  of  this  period,  the 
urine  and  faeces  were  collected  and  analyzed.  During  the  next  5 
days  it  became  possible  to  overcome  the  stenosis  by  means  of  a 
narrow  stomach  tube  and  the  administration  of  liquid  food,  milk 
and  eggs,  became  possible.  During  these  five  days  the  patient  re- 
ceived an  average  of  7.6  grams  of  nitrogen  per  day,  with  a  caloric 
supply  of  765  calories  per  day  (24  calories  per  kg.).  On  this  low 
diet  the  patient  retained  an  average  of  1.7  grams  of  nitrogen  per 
day. 


128     SCHAMBKRG,  KOLMER,  RIXGER,  AND  RAIZISS 

During  the  following  7  days  the  nitrogenous  intake  was  8.99 
grams  per  day  and  the  fuel  value  of  the  food  was  881  calories  per 
day  (27  calories  per  kg.).  The  nitrogen  retention  continued  to 
the  extent  of  1.9  grams  per  day. 

In  their  experiments  on  typhoid  convalescents,  Luthje  and  Ber- 
gcr  32  obtained  nitrogen  retentions  during  the  first  five  days  of  the 
experiment  in  a  patient  who  was  on  a  diet  containing  not  more  than 
38  calories  per  kg.  of  body  weight.  The  nitrogen  retention  was  to 
the  extent  of  3.5  grams  per  day.  We  do  not  include  their  other 
experiments  in  which  retentions  of  10  grams  of  nitrogen  per  day 
were  obtained,  because  the  caloric  supply  was  higher  than  the 
requirements. 

Benedict  and  Suranyi  33  carried  out  some  beautiful  experiments 
on  typhoid  convalescents  and  obtained  a  retention  of  237  grams 
of  nitrogen  in  the  course  of  33  days,  with  the  patient  on -a  diet  of 
approximately  3200  calories  per  day.  (Unfortunately,  the  pa- 
tient's exact  weight  is  not  given.) 

These  experiments  show  conclusively  the  differences  that  exist 
in  the  nitrogen-storing  capacities  of  the  normal  individual  and  the 
convalescent,  who  has  just  passed  through  a  prolonged  illness  asso- 
ciated with  undernutrition  and,  principally,  loss  in  body  protein. 
They  show  with  what  velocity  and  comparative  ease  the  conva- 
lescent's body  can  store  nitrogen  and,  also,  for  what  prolonged 
periods. 

NITROGEN  RETENTION  IN  PSORIASIS. 

When  we  come  to  examine  the  character  and  extent  of  the  nitro- 
gen retention  in  the  psoriatic  patient,  in  the  light  of  the  aforesaid, 
we  cannot  fail  to  observe  the  similarity  that  obtains  between  the 
behavior  of  the  psoriatic  and  that  of  the  convalescent,  with  refer- 
ence to  the  ease  with  which  each  can  store  nitrogen  in  large  quan- 
tities and  for  long  periods  of  time. 

The  continuous  storing  of  nitrogen  in  Patient  No.  3  resembles 
Benedict  and  Suranyi's  cases  in  almost  every  particular. 

The  retention  of  2.5  grams  of  nitrogen  per  day  in  Patient  No.  8, 
Period  3,  when  receiving  an  average  of  7.08  grams  of  nitrogen  and 
only  26.4  calories  per  kg.,  is  almost  an  exact  duplication  of  Fried- 
rich  Muller's  case,  which  was  certainly  in  a  very  bad  state  of 
undernutrition. 

When  we  add  to  this  our  experience  with  the  superimposed  milk 
feeding  of  500  and  1000  cc.,  fed  in  addition  to  a  standard  diet  and 
our  failure  to  find  any  evidence  of  catabolism  of  this  extra  nitrogen 


RESEARCH    STUDIES    IN    PSORIASIS  129 

in  the  urine,  we  feel  inclined  to  believe  that  patients  with  severe 
psoriasis  present  a  state  of  remarkable  protein  undernutrition, 
which  we  choose  to  call  "specific  nitrogen  hunger"  (see  page  130). 
Because  of  this  nitrogen  hunger,  they  possess  the  power  of  retaining 
nitrogen  to  a  most  marked  extent,  even  under  conditions  in  which 
a  normal  individual  would  find  difficulty  in  maintaining  equilibrium. 

The  following  questions  now  present  themselves:  Wherein  is  the 
cause  of  this  "nitrogen  hunger"  to  be  sought;  what  is  the  relation- 
ship between  the  psoriatic  lesion  and  the  nitrogen  hunger;  what 
causal  relationship  may  they  bear  to  each  other?  Then,  what  be- 
comes of  the  retained  nitrogen,  where  does  it  go,  and  in  what  form 
is  it  retained? 

Answers  to  these  questions  may  be  found  in  an  analysis  of  the 
results  obtained  in  Patient  No.  8  (Table  5),  in  Patient  No.  9,  and 
in  the  pathological  histology  of  the  psoriatic  lesion. 

Patient  No.  8  lived  in  the  hospital  under  our  observation  for 
a  period  of  44  days.  During  this  period  she  ingested  293.4  grams 
of  nitrogen.  For  the  same  period  she  eliminated  in  the  urine  and 
faeces,  210.6  grams,  leaving  an  apparent  positive  nitrogen  balance 
of  82.8  grams.  There  is  no  doubt  that  this  nitrogen  is  retained 
in  the  form  of  protein.  The  question  is,  where  is  it  retained? 

To  properly  understand  this  point,  we  must  recognize  a  very 
important  series  of  facts  which  deal  with  the  pathology  of  psoria- 
sis. Disregarding  the  differences  of  opinion  that  exist  with  regard 
to  the  seat  of  the  primary  lesion  of  psoriasis,  all  are  agreed  that 
there  are  evidences  of  inflammation  in  the  papillary  layer  of  the 
corium  and  that  the  rete  mucosum  is  hyperplastic.  The  epithelial 
cells  proliferate  with  great  velocity,  push  toward  th  surface,  become 
cornified  and  are  finally  exfoliated.  The  chief  constituents  of  these 
epithelial  cells  are  proteins,  which  must  be  obtained  by  the  cells 
from  the  blood.  To  realize  the  extent  to  which  this  proliferation 
may  occur  and  to  appreciate  the  amount  of  protein  that  may  thus 
be  removed  from  the  blood  and  ultimately  from  the  cells  of  the 
body,  we  shall  state  that  during  her  stay  in  the  hospital  we  col- 
lected 446  grams  of  scales,  exfoliated  by  this  patient's  skin,  and  this 
amount  does  not  represent  the  full  amount  of  scaling,  for  a  quanti- 
tative collection  is  almost  impossible  in  a  case  like  this,  because  of 
the  fineness  of  the  scales  and  the  difficulty  of  collection.  The  nitro- 
gen content  of  the  collected  scales  varied  from  11.8  to  14.4%. 
Almost  pure  protein!  The  total  amount  of  nitrogen  in  the  scales 
was  58.38  grams.  We  have  no  idea  how  much  nitrogen  this  patient 
lost  through  the  scales  before  she  came  to  the  hospital.  Judging 


130     SCHAMBERG,  KOLAIER,  RINGER,  AND  RAIZISS 

from  the  amounts  we  obtained,  the  total  loss  must  have  been 
enormous. 

In  what  way  does  the  loss  of  nitrogen  in  the  scales  influence 
the  total  nitrogen  metabolism  of  the  body?  This  question  is  an- 
swered very  clearly  in  the  following  experiment : 

Patient  No.  8,  who  scaled  very  profusely,  and  Patient  No.  9, 
who  scaled  only  moderately,  were  placed  on  the  same  diet  during 
the  period  of  May  80th  to  June  5th.  The  figures  for  the  week 
follow  : 

Patient      Weight       Nitrogen  Nitrogen  Nitrogen  Nitrogen  Net  nitrogen 

ingested  in  faeces  in  urine  in  scales  balance 

No.  8             58.4             30.70  13.78            13.16               8.75  —4.99 

No.  9              54.6             30.04  13.54            20.9-',               2.47  —651 

The  amount  of  nitrogen  ingested  and  the  amount  of  nitrogen  in  the 
faeces  were  similar  in  these  patients,  but  there  was  a  great  difference 
in  the  amounts  of  nitrogen  in  the  scales.  Patient  No.  8  lost  6.28 
grams  more  in  the  scales  than  Patient  No.  9  did,  and  she  eliminated 
7.78  grams  less  in  the  urine.  //  we  assume  the  nitrogen  in  the  urine 
to  represent  the  end  products  of  protein  metabolism  of  the  cells  of 
the  body,  we  see  very  clearly  to  what  an  extent  the  condition  of  the 
skin  influences  the  total  protein  metabolism.  The  proliferation  and 
rapid  growth  of  the  epithelial  cells  of  the  skin  deprive  the  cells  of  the 
body  of  their  nutrient  material  and  force  them  to  subsist  at  a  starva- 
tion level.  During  the  course  of  the  week  only  13.16  grams  of  nitro- 
gen were  eliminated  in  the  urine,  an  average  of  1.88  grams  per  day, 
or  0.0323  gram  per  kg.  of  body  weight.  This  is  the  very  lowest 
figure  that  has  ever  been  reported  for  an  individual  under  similar 
conditions  of  nutrition. 

The  proliferation  and  growth  of  epithelial  cells  takes  place 
throughout  the  entire  period  of  the  disease,  commencing,  in  all 
probability,  long  before  exfoliation  begins.  For  this  growth  of 
cells,  protein  is  required,  which  is  abstracted  by  the  multiplying 
epithelial  cells  from  the  blood  stream,  in  quantities  proportional 
to  the  severity  of  the  disease.  This  constant  drain  of  protein  from 
the  body  into  the  skin,  where  it  becomes  "fixed,"  gradually  causes 
the  impoverishment  of  the  body  in  protein  producing  a  condition  of 
"specific  nitrogen  hunger." 

If  at  any  time  during  this  process  a  study  of  the  protein  meta- 
bolism is  instituted,  nitrogen  retention  will  be  evident.  This  retained 
nitrogen  can  go  in  one  or  in  two  places,  depending  upon  the  stage 
of  the  disease  and  upon  the  protein  status  of  the  patient.  It  may 


RESEARCH    STUDIES    IN    PSORIASIS  131 

be  carried  to  the  epithelium  of  the  skin  to  become  incorporated 
in  the  proliferating  cells  and  finally  be  given  off  as  exfoliated  scales, 
or  it  may  be  carried  to  the  cells  of  the  body,  especially  to  the  muscle 
cells,  which  have  become  impoverished  of  their  protein.  The  nitro- 
gen may  be  deposited  in  the  muscle  cells  of  a  psoriatic  patient,  as  it 
is  in  a  convalescent  patient  after  a  prolonged  illness.  In  both 
classes  of  patients  a  positive  nitrogen  balance  takes  place. 

This  theory  seems  to  be  in  harmony  with  many  of  the  facts  and 
seems  to  explain  the  cause  of  the  remarkable  and  prolonged  nitrogen 
retentions. 

INFLUENCE  OF  A  Low  PROTEIN  DIET  ox  THE  COURSE  OF  PSORIASIS. 

On  carefully  reviewing  the  clinical  histories  of  our  patients,  one 
cannot  fail  to  notice  that  the  low  protein  diet  exercised  a  distinctly 
beneficial  influence  on  the  course  of  the  disease.  Conversely,  a  high 
protein  diet  had  a  strong  tendency  to  exacerbate  the  condition. 

How  can  we  explain  these  relationships?  In  what  way  can  we 
conceive  of  the  low  protein  diet  influencing  the  patient's  skin? 

Bulkley,84  who  long  ago  recognized  the  favorable  influence  of  a 
low  protein  or  vegetarian  diet  on  the  course  of  psoriasis,  endeavored 
to  construct  a  theory  of  disturbed  protein  catabolism.  He  deserves 
credit  for  his  recognition  of  the  influence  of  various  dietary  regimes 
on  the  course  of  the  disease.  The  analytical  data,  however,  upon 
which  his  theory  is  based  would  not  stand  scrutiny  in  the  light  of 
modern  scientific  and  experimental  research. 

We  believe  that  the  following  consideration  offers  a  satisfactory 
explanation : 

One  of  the  most  prominent  features  of  the  histology  of  psoriasis 
is  the  rapid  growth  and  proliferation  of  the  epithelial  cells  of  the 
skin.  For  the  present,  we  may  leave  out  of  consideration  the 
primary  aetiologic  factor.  But  one  thing  must  be  clearly  understood : 
for  their  growth  and  life,  these  cells  require  building  material,  which 
can  be  obtained  from  only  one  source — the  blood  and  lymph  streams. 
The  principal  building  material  required  by  these  cells  is  protein. 
It  is  at  once  evident  that  since  these  cells  are  endowed  with  a  power- 
ful "growth  impulse,"  "Wachstumstrieb,"  the  velocity  of  their 
growth  will  be  directly  proportional  to  the  amount  of  "building 
material"  in  the  form  of  protein,  that  is  placed  at  their  disposal. 
A  high  protein  diet  therefore  stimulates  their  growth,  because  it  pro- 
vides all  the  necessary  components  of  the  epithelial  cells. 

By  keeping  the  patient  on  a  low  protein  diet,  on  an  amount 


132     SCHAMHKKG,  KOLMKR,  RINGKR,  AND  RAI/ISS 

just  enough  to  cover  the  body's  "wear  and  tear"  quota,  we  bring 
about  a  condition  in  which  no  extra  protein  can  be  supplied  to  the 
rapidly  multiplying  cells  of  the  skin.  If  the  "growth  impulse"  of 
these  cells  were  not  so  great,  this  point  would,  in  all  probability, 
mark  the  end  of  the  disease.  May  it  not  be  possible  therefore,  that 
the  rapidly  growing  cells  in  psoriasis,  like  those  of  malignant  growths, 
have  the  power  of  preying  on  the  rest  of  the  body,  withdrawing 
protein  from  the  blood,  and  then  the  blood  in  turn  attacks  the  pro- 
tein storehouses — the  muscles?  This  may  go  on  for  a  long  time  until 
the  body's  protein  reserve  is  exhausted,  when  the  growth  of  the 
epithelial  cells,  patches  and  scalings  becomes  checked.  A  similar 
process  has  been  described  in  the  classic  researches  of  Miescher.35 
He  found  that  during  the  salmons'  migration  up  the  Rhine,  they  suf- 
fer from  complete  starvation.  During  this  period  their  genital  or- 
gans become  remarkably  proliferated,  whereas  the  muscles  lose  up 
to  50%  of  their  protein  content.  This  is  an  illustration  of  the 
rapid  growth  of  one  tissue  at  the  expense  of  another  in  a  starving 
animal.  The  high  "growth  impulse"  of  the  testicular  tissue  is  the 
determining  factor. 

In  the  psoriatic  patient  the  same  thing  may  take  place,  but  to  a 
lesser  degree.  The  epithelial  cells  of  the  skin  keep  on  growing  as 
long  as  there  is  "available"  or  "mobilizable"  protein  in  the  system. 
When  this  is  exhausted,  their  growth  is  checked.  And  this,  in  our 
estimation,  may  account  for  the  frequent  spontaneous  improve- 
ments in  cages  of  psoriasis.  By  keeping  the  patient  on  a  low  protein 
diet,  we  hasten  this  point  of  "exhaustion."  We  hasten  the  slow 
starvation  of  the  epithelial  cells.  By  keeping  the  patient  on  a  high 
protein  diet,  we  stimulate  the  growth  of  the  epithelial  cells  and  thus 
delay  improvement.  (See  Patient  No.  7.) 

We  find  additional  support  for  this  theory  in  the  following 
clinical  observations  of  S.  Jessner:36  "Von  altersher  herrscht  die 
Anschauung,  dass  die  Psoriasis  vornehmlich  Kraftige,  muskulose, 
sonst  gesunde  Individuen  befallt.  Dies  ist  im  allgemeinen  richtig, 
wenn  auch  Ausnahmen  nicht  allzu  selten  sind..  Zuweilen  kann  man 
feststellen,  dass  bei  kraftigen  Personen  eine  vorhandene  Psoriasis 
schwindet,  sobald  sie  von  einer  schwereren  Krankheit  heimgesucht 
werden  und  Korperlich  herunterkommen.  Erholen  sie  sich  spater, 
dann  erscheint  die  Psoriasis  wieder  auf  die  Bildflache." 

Similar  observations  have  been  recorded  by  various  writers  who 
have  reported  the  disappearance  of  psoriasis  in  patients  suffering 
from  acute  infections,  only  to  return  after  the  infectious  disease  has 
subsided. 


RESEARCH    STUDIES    IN    PSORIASIS  133 

These  facts  lend  support  to  our  theory,  because  they  show  that 
every  condition  that  is  associated  with  increased  protein  catabolism 
or  diminished  protein  ingestion  results  in  improvement  of  the 
psoriasis. 

An  analogy  was  previously  drawn  between  malignant  growths 
and  the  growth  of  the  epithelial  cells  in  psoriasis.  Biologically, 
the  two  seem  to  have  a  great  deal  in  common.  The  difference  ap- 
pears to  be  one  of  degree  only.  Both  are  endowed  with  great  growth 
impulse  and  power  of  proliferation,  both  have  the  power  of  living 
on  and  multiplying  at  the  expense  of  the  cells  of  the  host.  The 
difference  between  the  two  is  that  by  exhausting  the  reserve  depots 
of  protein,  the  psoriasis  will  always  be  checked  because  its  "growth 
impulse"  is  not  as  great  as  is  that  of  the  malignant  tumors,  which 
will  go  on  growing  until  they  bring  about  a  toxic  disruption  of  the 
cells  of  the  host.  Powerful  as  is  the  action  of  malignant  tumors  in 
this  respect,  it  was  recently  shown  by  J.  E.  Sweet,  Corson- White  and 
Saxon,  in  a  beautiful  research,37  that  even  the  growth  of  adeno- 
carcinoma  of  the  rat  and  carcinoma  of  mice  may  be  checked  by  an 
improper  and  insufficient  protein  supply. 

THE  RELATIONSHIP  BETWEEN  RETAINED   NITROGEN  AND  GAIN  IN 

BODY  WEIGHT. 

On  examining  the  influence  of  nitrogen  retention  on  the  body 
weight  of  our  patients,  we  found  that  in  most  cases  there  was  no 
relationship  at  all;  that  the  retention  of  even  large  quantities  of 
nitrogen  may  not  be  accompanied  by  any  gain  in  weight. 

On  admission  to  the  hospital,  Patient  No.  3  weighed  40.85  kg. 
When  she  left,  after  a  stay  of  128  days,  she  weighed  42.2  kg.  Dur- 
ing this  period,  she  retained  a  net  amount  of  402  grams  of  nitro- 
gen, which  is  contained  in  2512  grams  of  pure  protein.  Her  body 
weight  should  have  increased  by  at  least  that  amount,  leaving  aside 
the  amount  of  water  that  would  be  necessary  to  dissolve  the  protein 
to  the  consistency  of  the  cell.  A  similar  lack  of  proportion  was 
found  in  Patients  No.  4  and  No.  5.  But  Patient  No.  7,  who  was  kept 
on  a  high  protein  diet  throughout  the  course  of  the  experiment, 
retained  286  grams  of  nitrogen — 1.79  kg.  of  protein.  During  this 
same  period,  the  patient  gained  1.4  kg.  in  weight. 

Observations  of  this  kind  are  not  new  in  physiological  literature. 
Bischoff  and  Voit38  recorded  them  as  early  as  1860,  but  thai  the 
lack  of  proportion  could  be  as  great  as  was  observed  in  Patient 
No.  3  was  most  surprising. 


134     SCHAMBERG,  KOLiMER,  RINGER,  AND  RAIZISS 

Bischoff  and  Voit30  fed  a  dog  on  bread  for  41  days  and  during 
this  period  the  animal  lost  an  amount  of  protein  corresponding  to 
3717  grams  of  flesh.  The  total  loss  of  body  weight,  however,  was 
only  531  grams.  The  difference  was  made  up  by  retention  of  water. 
As  the  animal's  state  of  nutrition  began  to  improve  by  the  ingestion 
of  1800  grams  of  meat  per  day,  the  water  was  rapidly  eliminated. 
The  results  obtained  on  the  first  day  of  the  meat  feeding  are  very 
interesting.  In  spite  of  this  tremendous  food  intake  the  animal  lost 
310  grams  in  weight  and  the  urine  itself  contained  120  cc.  more 
water  than  was  ingested. 

Very  striking,  also,  is  Liithje  and  Berger's40  experiment  No.  3, 
in  which  their  subject  received  food  with  a  fuel  value  of  72  calories 
per  kg.,  and  49.6  grams  of  nitrogen  per  day.  The  amount  of 
nitrogen  retained  per  day  was  11.4  grams  and  the  amount  of  fat 
that  was  stored  must  have  amounted  to  at  least  200  grams  per  day. 
In  the  first  four  days  there  was  a  retention  of  at  least  800  grams  of 
fat  and  285  grams  of  protein,  1085  grams  of  material  in  all,  and  in 
spite  of  this  retention,  the  subject's  weight  was  0.6  kg.  less  than  when 
the  experiment  started. 

This  lack  of  relationship  between  an  actual  gain  in  body  material 
and  a  failure  to  show  it  in  a  gain  of  body  weight,  can  be  accounted 
for  by  assuming  a  variation  in  the  amount  of  water  in  the  tissu'es. 
That  the  relative  amount  of  solid  material  decreases  in  muscle  tissue 
in  starvation,  was  shown  definitely  in  Rubner's  laboratory.41 

The  following  changes  were  found  in  the.  muscle  of  fasting 
animals : 

Normal  Fasting 

Solid  Water  Solid  Water 

22.87  77.13  18.73  81.27 

23.65  76.35  17.99  82.01 

Average    23.26  76.74  18.36  81.6!t 

This  table  shows  very  plainly  that  in  starvation  the  relative 
amounts  of  water  may  increase  very  considerably.  Of  course,  we 
must  bear  in  mind  that  our  patients  did  not  suffer  from  any  de- 
privation of  food,  but  from  specific  nitrogen  hunger.  What  the 
influence  of  this  condition  may  be  on  the  water  content  of  the  cells 
will  be  the  subject  of  our  inquiry  in  the  immediate  future. 

RESUME  OF  THE  CLINICAL  RESULTS. 

The  primary  purpose  of  our  physiological  studies  was  to  ascer- 
tain whether  any  deviation  from  normal  occurred  in  the  metabolism 
of  psoriasis  patients.  We  have  seen  that  a  disturbance  of  the  nitro- 


RESEARCH    STUDIES    IN    PSORIASIS  135 

gen  metabolism  does  exist  in  psoriasis,  more  particularly  in  severe 
cases.  We  have  demonstrated  that  such  patients  quite  constantly 
retain  nitrogen  and  that  this  element  is  needed  for  the  proliferation 
of  the  epithelial  cells  of  the  skin.  Indeed,  without  a  bountiful  supply 
of  protein  from  the  blood  and  tissue  juices,  such  rapid  cellular 
growth  as  occurs  in  psoriasis  would  be  impossible. 

We  felt,  therefore,  that  an  eminently  important  as  well  as  practi- 
cal aspect  of  our  studies  was  to  note  the  effect  on  the  psoriasis 
eruption  of  diets  containing  different  amounts  of  nitrogen.  Such 
observations  require  adequate  time  for  each  experiment,  as  a  dietary 
regime  continued  for  only  a  short  period  might  readily  lead  to  con- 
fusion of  interpretation.  From  our  observations,  we  are  strongly 
inclined  to  believe  that  a  high  or  even  relatively  high  nitrogen  diet 
has  a  baneful  influence  on  psoriasis.  In  four  of  our  patients  (Cases 
3,  4,  5  and  7),  in  whom  this  experiment  was  tried,  an  aggravation  of 
the  eruption  occurred.  With  the  exception  of  one  patient  (Case 
7),  it  was  impossible  to  continue  the  high  nitrogen  diet  for  a  pro- 
longed period,  owing  to  the  fact  that  we  could  not  interne  our  pa- 
tients in  the  hospital  for  a  sufficient  period  of  time- and,  moreover, 
because  of  the  prejudices  of  the  patients  who  feared  the  influence  of 
such  a  diet.  In  Case  3,  a  rapid  extension  of  the  psoriasis  occurred 
in  the  early  days  of  her  hospital  sojourn,  while  she  was  taking  a 
relatively  high  amount  of  nitrogen.  Many  weeks  later,  after  marked 
improvement  had  taken  place,  so  that  but  insignificant  vestiges  of 
the  disease  remained,  a  high  nitrogen  diet  was  resumed  for  several 
weeks  without  apparent  harm;  at  this  time,  however,  the  patient 
was  eliminating  nitrogen  better  than  at  any  period  of  our  observa- 
tion. Whether  one  can  stimulate  the  outbreak  of  psoriasis  in  a 
psoriatic  patient  free  of  the  eruption,  we  have  not  had  the  oppor- 
tunity of  determining.  We  shall  continue  our  observations  on  the 
influence  of  a  high  nitrogen  diet  upon  psoriasis  patients  in  order 
to  settle  this  question. 

We  were  in  a  better  position  to  determine  the  influence  of  a  low 
nitrogen  diet  upon  the  activity  of  the  psoriatic  process,  because  of 
the  fuller  cooperation  of  our  patients.  Although  this  diet  meant 
a  greater  deprivation  of  articles  of  food  to  which  they  were  accus- 
tomed, still  they  preferred  this  regime,  as  in  their  own  opinion  it 
was  conducive  to  their  improvement.  We  feel  that  there  can  exist 
little  doubt  as  to  the  favorable  influence  of  a  low  nitrogen  diet  on  the 
eruption  of  psoriasis.  This  is  more  strikingly  seen  in  severe  cases, 
for  in  such  patients  improvement  is  more  rapidly  and  readily  evident. 
In  support  of  our  conclusion,  we  place  in  evidence  the  photographic 


136     SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

records  of  Cases  3,  5,  6  and  8,  in  whom  the  improvement  was  strik- 
ing if,  indeed,  not  remarkable.  It  would  appear  that  the  milder  the 
case,  i.e.,  the  more  limited  the  eruption,  the  less  pronounced  and  the 
less  immediate  is  the  influence  of  a  low  nitrogen  diet.  Some  of  our 
mild  cases  exhibited  only  a  moderate  degree  of  improvement. 

It  is  well  known  that  psoriasis  is  a  disease  subject  to  variations, 
both  improvement  and  exacerbation,  without  known  cause.  The 
question  might  pertinently  be  asked  whether  the  improvement  could 
not  have  been  mere  coincidence,  or,  whether  other  factors  could  not 
have  been  responsible  for  the  improvement  observed.  We  have  many 
times  asked  ourselves  this  question.  It  would  be  difficult  to  account 
for  our  results  on  the  basis  of  pure  coincidence.  The  sequence  of 
events  was  too  direct  and  the  number  of  striking  improvements 
reached  too  high  a  proportion  to  admit  of  such  an  explanation. 
Furthermore,  all  must  concede  that  the  changes  for  better  or  worse 
in  psoriasis  are  not  in  reality  spontaneous  merely  because  they  occur 
without  apparent  cause. 

After  carefully  studying  our  patients  and  thoroughly  scrutinizing 
all  of  the  environmental  conditions,  we  have  been  forced  to  eliminate 
the  latter  as  influencing  factors.  It  will  be  recalled  that  Case  7  was 
studied  as  a  control  in  order  to  determine  whether  freedom  from  phys- 
ical labor  and  from  mental  harassment,  in  a  quiet  private  room  in  a 
hospital,  could  have  accounted  for  the  improvement  in  some  of  the 
other  patients.  But  this  patient  (who  was  placed  on  a  high  nitrogen 
diet)  was,  after  84  days  residence  in  the  hospital,  worse  than  upon 
admission.  It  is  interesting  here  to  note  that  this  patient  made 
decided  improvement  with  respect  to  the  nervous  disorder  (chorea) 
from  which  he  was  suffering,  at  the  same  time  that  his  psoriasis 
was  growing  gradually  worse.  This  observation  does  not  lend  any 
support  to  the  theory  of  the  neuropathic  origin  of  the  disease,  which 
is  held  by  a  number  of  writers.  On  the  other  hand,  Patient  No.  3, 
was  frequently  in*  a  highly  nervous  and  apprehensive  state,  with 
numerous  crying  spells  and  periods  of  depression,  and  yet  her  erup- 
tion improved  to  the  point  of  virtual  disappearance. 

In  Figs.  23  and  24  are  contrasted  the  eruptions  in  the  case  of  a 
young  man  who  was  treated  in  the  dispensary.  He  received  no  in- 
ternal or  external  treatment  of  any  kind  whatsoever,  but  was  placed 
upon  a  low  nitrogen  diet,  which  he  faithfully  carried  out.  The 
eruption  entirely  disappeared  in  two  months,  leaving  pigmented 
spots  which  subsequently  faded  away.  The  second  photograph  was 
taken  in  the  month  of  May. 

The  enormous  proliferation  of  the  epithelial  cells   of  the  rete 


PLATE  XXXIX.— To  Illustrate  Article  on  Research  Studies  in  Psoriasis, 
bv  DHS.   SCIIAMBERG,   Koi.MER,   RINGER   and   RAIZISS. 


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THE  JOURNAL  OF  CUTANEOUS  DISEASES,  November,  1913. 


RESEARCH    STUDIES    IX    PSORIASIS  137 

mucosum  in  psoriasis  and  their  exfoliation  from  the  skin  after  they 
have  been  cornified,  creates  a  great  demand  for  protein.  This  pro- 
tein can  only  be  supplied  through  the  blood  and  lymph  streams. 
The  diverting  of  the  food  protein  to  this  purpose  naturally  lessens 
the  amount  catabolized  in  the  system  and  eliminated  in  the  excreta. 
Nitrogen  retention  may  in  considerable  part  be  explained  by  the  loss 
of  protein  through  scaling.  But  this  does  not  explain  the  entire 
retention  because  (1)  the  deficit  of  nitrogen  in  the  excreta  is  greater 
than  can  be  accounted  for  by  the  amount  lost  through  the  skin ;  and 
(2)  we  have,  in  a  most  thoroughly  studied  case,  observed  a  consider- 
able retention  of  nitrogen  after  the  scaling  had  ceased  and  the  erup- 
tion had  virtually  disappeared. 

This  retention  is  difficult  to  account  for.  It  is  possible  that  the 
skin,  during  its  great  proliferative  activity,  may  call  upon  the  mobi- 
lizable  protein  in  the  muscles  and  other  tissues  and  that,  later,  this 
reserve  protein  may  be  restored  from  the  food  protein  ingested. 

A  nitrogen  retention  having  been  established  to  exist  in  psoriasis, 
the  question  presents  itself — is  the  nitrogen  retention  primary  and 
to  be  regarded  as  the  astiological  factor,  or  one  of  the  astiological 
factors  in  the  causation  of  the  disease,  or  is  it  secondary  to  the 
pathological  changes  in  the  skin?  This  question  cannot  be  definitely 
settled  at  this  stage  of  our  investigations,  although  the  latter 
proposition  appears  to  be  more  in  harmony  with  the  demonstrated 
facts. 

In  the  present  stage  of  our  research  studies  we  are  unable  to  set 
up  an  hypothesis  as  to  the  cause  of  the  disease  without  departing 
from  the  domain  of  fact  and  entering  the  realm  of  conjecture.  We 
are  content  to  present  our  laboratory  findings  and  set  forth  the  re- 
sults of  our  clinical  observations.  We  are  still  in  the  midst  of  our 
pathological  and  metabolic  studies  and  many  problems  must  be 
solved  before  any  definite  pronouncement  as  to  the  nature  and  cause 
of  psoriasis  can  be  safely  made. 

SUMMARY  AND  CONCLUSIONS. 

A  careful  study  was  made  of  the  protein  metabolism  of  eight 
psoriasis  patients  and  the  following  observations  were  made: 

1.  That  on  a  given  protein  diet  a  psoriatic  subject  eliminates 
less  nitrogen  in  the  urine  than  does  a  normal  individual  on  a  cor- 
responding diet.     The   urinary  nitrogen  in  some  of  our  patients 
reached  a  level  lower  than  has  ever  been  recorded. 

2.  Patients   suffering   from  psoriasis   exhibit   a  remarkable   re- 


138     SCHAMBERG,  KOLMER,  RINGER,  AND  RAIZISS 

tention  of  nitrogen.  This  retention  appears  to  be  proportional,  in 
a  general  way,  to  the  extent  and  severity  of  the  eruption  present. 
8.  The  nitrogen  is  retained  to  a  greater  degree  than  has  been 
observed  in  connection  with  any  other  condition  and  is,  furthermore, 
retained  with  great  ease  even  on  a  diet  low  in  nitrogen  and  insuffi- 
cient in  caloric  value,  and  one  on  which  a  normal  individual  would 
fail  to  maintain  equilibrium. 

4.  Experiments  with  urea  feedings  show  conclusively  that  the 
nitrogen  retention  cannot  be  attributed  to  any  disturbance  in  the 
eliminative  capacity  of  the  kidneys. 

5.  Patients  with  extensive  psoriasis  may  lose  very  large  amounts 
of  nitrogen  in  the  exfoliated  scales,  which  consist  of  almost  pure 
protein. 

6.  The  retention  of  nitrogen  in  most  of  our  cases  was  greater 
than  could  be  accounted  for  by  the  protein  lost  in  the  scales,  and 
it  may  persist  even  after  scaling  has  ceased  and  the  eruption  has 
virtualjy  disappeared. 

7.  A  low  nitrogen  diet  has  a  most  favorable  influence  upon  the 
eruption  of  psoriasis,  particularly  when  the  latter  is  extensive.  Mak- 
ing all  reservation  suggested  by  scientific  caution,  we  feel  that  there 
can  be  no  doubt  that  severe  cases  of  psoriasis  improve  under  such 
a  diet,  almost  to  the  point  of  disappearance  of  the  eruption. 

8.  Conversely,  a  high  nitrogen  diet  exhibits  an  unfavorable  in- 
fluence on  psoriasis,  commonly  causing  an  extension  of  the  eruption. 

9.  Whether  a  high  nitrogen  diet  can  stimulate  an  outbreak  of 
psoriasis  in  a  psoriatic  subject,  who  is  at  the  time  free  of  the  erup- 
tion, has  not  yet  been  determined. 

10.  The  great  proliferation  and  exfoliation  of  cells  by  the  skin 
in  psoriasis  demand  a  large  supply  of  protein,  which  can  only  be 
procured  from  the  lymph  and  blood  streams.     This  protein  supply 
may  be  derived  from  the  ingested  food,  and  a  possibility  exists  that 
the  great  demand  of  the  diseased  skin  for  protein  may  also  be  satis- 
fied by  the  protein  reserve  in  muscle  tissue,  which  thus  may  become 
depleted   and   later   require   restoration.     This   would    explain    the 
ready  and  persistent  retention  of  nitrogen  in  our  cases. 

11.  A  protracted,  low  protein  diet  may  diminish  the  prolifera- 
tive  activity  of  the  skin  by  diminishing  the  supply  of  the  principal 
building  material,   namely,  protein.     On   the  other  hand,   a  high 
protein  diet  may   stimulate  the  proliferative   activity   of  the  cells 
by  furnishing  an  abundant  supply  of  the  necessary  protein. 

12.  We  deem  it  premature  at  the  present  stage  of  our  studies 
to  commit  ourselves  to  an  hypothesis  as  to  the  primary  cause  of 


RESEARCH    STUDIES    IN    PSORIASIS  139 

psoriasis.     Our  studies  are  being  continued  and  extended  in  various 
directions. 

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140     SCHAAIBERG,  KOLMER,  RINGER,  AND  RAIZISS 

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